Objective This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1)in the development of hepatocellular carcinoma(HCC).Methods A total of 62 pairs of HCC tissues and adjacent non-t...Objective This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1)in the development of hepatocellular carcinoma(HCC).Methods A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients.The interactions of PCED1B-AS1 and microRNA-34a(miR-34a)were detected by dual luciferase activity assay and RNA pull-down assay.The RNA expression levels of PCED1B-AS1,miR-34a and CD44 were detected by RT-qPCR,and the protein expression level of CD44 was determined by Western blotting.The cell proliferation was detected by cell proliferation assay,and the cell invasion and migration by transwell invasion assay.The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study.Results PCED1B-AS1 was highly expressed in HCC tissues,which was associated with poor survival of HCC patients.Furthermore,PCED1B-AS1 interacted with miR-34a in HCC cells,but they did not regulate the expression of each other.Additionally,PCED1B-AS1 increased the expression level of CD44,which was targeted by miR-34a.The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro,while CD44 exhibited the opposite effects.Furthermore,PCED1B-AS1 suppressed the role of miR-34a.Moreover,the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo.Conclusion PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and aggressive tumor.Sorafenib is the first-line treatment for patients with advanced HCC,but resistance to sorafenib has become a significant challenge in this t...BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and aggressive tumor.Sorafenib is the first-line treatment for patients with advanced HCC,but resistance to sorafenib has become a significant challenge in this therapy.Cancer stem cells play a crucial role in sorafenib resistance in HCC.Our previous study revealed that the long non-coding RNA(lncRNA)KIF9-AS1 is an oncogenic gene in HCC.However,the role of KIF9-AS1 in drug resistance and cancer stemness in HCC remains unclear.Herein,we aimed to investigate the function and mechanism of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC.AIM To describe the role of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC and elucidate the underlying mechanism.METHODS Tumor tissue and adjacent non-cancerous tissue samples were collected from HCC patients.Sphere formation was quantified via a tumor sphere assay.Cell viability,proliferation,and apoptosis were evaluated via Cell Counting Kit-8,flow cytometry,and colony formation assays,respectively.The interactions between the lncRNA KIF9-AS1 and its downstream targets were confirmed via RNA immunoprecipitation and coimmunoprecipitation.The tumorigenic role of KIF9-AS1 was validated in a mouse model.RESULTS Compared with that in normal controls,the expression of the lncRNA KIF9-AS1 was upregulated in HCC tissues.Knockdown of KIF9-AS1 inhibited stemness and attenuated sorafenib resistance in HCC cells.Mechanistically,N6-methyladenosine modification mediated by methyltransferase-like 3/insulin-like growth factor 2 mRNA-binding protein 1 stabilized and increased the expression of KIF9-AS1.Additionally,KIF9-AS1 increased the stability and expression of short stature homeobox 2 by promoting ubiquitin-specific peptidase 1-induced deubiquitination.Furthermore,depletion of KIF9-AS1 alleviated sorafenib resistance in a xenograft mouse model of HCC.CONCLUSION The N6-methyladenosine-modified lncRNA KIF9-AS1 promoted stemness and sorafenib resistance in HCC by upregulating short stature homeobox 2 expression.展开更多
BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 p...BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.展开更多
BACKGROUND： The majority of mammalian genomes have been found to be transcribed into non-coding RNAs. One category of non-coding RNAs is classified as long non-coding RNAs （lncRNAs） based on their transcript sizes ...BACKGROUND： The majority of mammalian genomes have been found to be transcribed into non-coding RNAs. One category of non-coding RNAs is classified as long non-coding RNAs （lncRNAs） based on their transcript sizes larger than 200 nucleotides. Growing evidence has shown that lncRNAs are not junk transcripts and play regulatory roles in multiple aspects of biological processes. Dysregulation of lncRNA expression has also been linked to diseases, in particular cancer. Therefore, studies of lncRNAs have attracted significant interest in the field of medical research. Nuclear enriched abundant transcript 1 （NEAT1）, a nuclear lncRNA, has recently emerged as a key regulator involved in various cellular processes, physiological responses, developmental processes, and disease development and progression. OBJECTIVE： This review will summarize and discuss the most recent findings with regard to the roles of NEAT1 in the function of the nuclear paraspeckle, cellular pathways, and physiological responses and processes. Particularly, the most recently reported studies regarding the pathological roles of deregulated NEAT1 in cancer are highlighted in this review. METHODS： We performed a systematic literature search using the Pubmed search engine. Studies published over the past 8 years （between January 2009 and August 2016） were the sources of literature review. The following keywords were used： ＂Nuclear enriched abundant transcript 1,＂ ＂NEATI,＂ and ＂paraspeckles.＂ RESULTS： The Pubmed search identified 34 articles related to the topic of the review. Among the identified literature, 13 articles report findings related to cellular functions of NEAT1 and eight articles are the investigations of physiological functions of NEAT1. The remaining 13 articles are studies of the roles of NEAT1 in cancers. CONCLUSION： Recent advances in NEAT1 studies reveal the multifimctional roles of NEAT1 in various biological processes, which are beyond its role in nuclear paraspeckles. Recent studies also indicate that dysregulation of NEAT1 function contributes to the development and progression of various cancers. More investigations will be needed to address the detailed mechanisms regarding how NEAT1 executes its cellular and physiological functions and how NEAT1 dysregulation results in tumorigenesis, and to explore the potential of NEAT1 as a target in cancer diagnosis, prognosis and therapy.展开更多
Changes in the abundance and activity of long non-coding RNAs(lncRNAs)have an important impact on the development of cancer.The nuclear paraspeckle assembly transcript 1(NEAT1)has been reported to be overexpressed in ...Changes in the abundance and activity of long non-coding RNAs(lncRNAs)have an important impact on the development of cancer.The nuclear paraspeckle assembly transcript 1(NEAT1)has been reported to be overexpressed in many types of cancer since its discovery.However,inconsistencies exist as NEAT1 can also function as a tumor suppressor in certain types of cancer,such as acute promyelocytic leukemia.Here we systematically describe our current understanding of NEAT1 in tumor initiation and progression.First,we analyzed the expression patterns of NEAT1 in various normal tissues and malignant cancers using data from public data portals,the Genotype-Tissue Expression Project(GTEx)and the Cancer Genome Atlas(TCGA),together with recent progress in the study of NEAT1 in various types of cancer.Second,we discussed the functions and mechanisms of NEAT1 in modulating tumor activity.Then,the upstream transcription factors and downstream microRNA targets of NEAT1 in the transcription cascade of cancers were also summarized.These data highlight the emerging role of NEAT1 in tumorigenesis,and present promising targetable pathways and clinical opportunities for tumor prevention and classifications.展开更多
Non-alcoholic fatty liver disease(NAFLD)is emerging as a common cause of chronic liver disease in children and adults.NAFLD can progress to steatohepa-titis and potentially even hepatocellular carcinoma.Early identifi...Non-alcoholic fatty liver disease(NAFLD)is emerging as a common cause of chronic liver disease in children and adults.NAFLD can progress to steatohepa-titis and potentially even hepatocellular carcinoma.Early identification of pati-ents at risk for progressive disease is crucial for managing NAFLD.Recent studies have identified long noncoding RNAs(lncRNAs),circular RNAs,and microRNAs as playing important roles in the pathogenesis of NAFLD.These noncoding RNAs are involved in modulating several metabolic pathways such as hepatic glucose and lipid metabolism,oxidative stress,and even carcinogenesis.Elevated levels of lncARSR and lncRNA nuclear-enriched abundant transcript 1 have been found in patients with NAFLD.In addition,lncRNAs such as PRYP4-3 and RP11-128N14.5 can distinguish patients with NAFLD from healthy indi-viduals.Increased MEG3 expression has been observed in both NAFLD and non-alcoholic steatohepatitis,suggesting that it may help predict patients at risk for disease progression.With advances in transcriptomics,we may discover additional targets to help in the identification and prognostication of NAFLD.展开更多
BACKGROUND Esophageal cancer is a common digestive tract tumor that is generally treated with radiotherapy.Poor responses to radiotherapy in most patients generally result in local radiotherapy failure,so it is essent...BACKGROUND Esophageal cancer is a common digestive tract tumor that is generally treated with radiotherapy.Poor responses to radiotherapy in most patients generally result in local radiotherapy failure,so it is essential to find new radiosensitizers that can enhance the response of cancer cells to radiotherapy and improve the survival of esophageal cancer patients with radiation resistance.The long noncoding RNA(lncRNA)Rpph1 is highly expressed in human gastric cancer tissues,and represses breast cancer cell proliferation and tumorigenesis.However,the expression of lncRNA Rpph1 in esophageal cancer and its relationship with radio-sensitivity has not been studied.AIM To explore the value of lncRNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy.METHODS Eighty-three patients with esophageal cancer admitted to Qilu Hospital of Shandong University and 90 healthy participants who received physical examinations were collected as research participants.The expression of Rpph1 was determined by qRT-PCR.siRNA-NC and siRNA-Rpph1 were transfected into esophageal cancer cell lines,and cells without transfection were designated as the blank control group.Cell survival was tested by colony formation assays,and the levels of proteins related to apoptosis and epithelial-mesenchymal transitions were determined by Western blot assays.Cell proliferation was assessed by MTT assays,cell apoptosis by flow cytometry,and cell migration by wound-healing assays.Changes in cell cycle distribution were monitored.RESULTS Rpph1 was highly expressed in esophageal carcinoma,making it a promising marker for the diagnosis of esophageal cancer.Rpph1 could also be used to distinguish different short-term responses,T stages,N stages,and clinical stages of esophageal cancer patients.The results of 3-year overall survival favored patients with lower Rpph1 expression over patients with higher Rpph1 expression(P<0.05).In vitro and in vivo experiments showed that silencing Rpph1 expression led to higher sensitivity of esophageal cancer cells to radiotherapy,stronger apoptosis in esophageal cancer cells induced by radiotherapy,higher expression of Bax and caspase-3,and lower expression of Bcl-2(Bax,caspase-3,and Bcl-2 are apoptosis-related proteins).Additionally,silencing Rpph1 attenuated radiation-induced G2/M phase arrest,and significantly inhibited the expression of proteins involved in cell proliferation,migration,and epithelial-mesenchymal transition regulation in esophageal cancer cells.CONCLUSION Rpph1 is highly expressed in esophageal cancer.Silencing Rpph1 expression can promote cell apoptosis,inhibit cell proliferation and migration,and increase radio-sensitivity.展开更多
Objective: Long non-coding RNAs(lnc RNAs) are involved in numerous biological processes in lung cancer cells. In our previous studies, we identified a lnc RNA, ENST00000439577, which is highly expressed in lung carcin...Objective: Long non-coding RNAs(lnc RNAs) are involved in numerous biological processes in lung cancer cells. In our previous studies, we identified a lnc RNA, ENST00000439577, which is highly expressed in lung carcinomas, and termed it lung cancer progression-associated transcript 1(LCPAT1). To characterize the role of LCPAT1 in lung cancer, we conducted the current study.Methods: Expression of LCPAT1 and autophagy-associated markers in tumor tissues and lung cancer cell lines was determined by real-time quantitative polymerase chain reaction(q PCR). Hematoxylin and eosin(HE) staining, q PCR, Western blot, and immunohistochemistry were performed to evaluate xenografted tumor tissues. Autophagy induced by rapamycin was detected by Western blot and immunofluorescence in lung cancer cell lines.Results: Expression of LCPAT1 and microtubule-associated protein 1 light chain 3 beta(LC3B) was positively correlated in lung cancer. Knockdown of LCPAT1 inhibited tumor growth and suppressed cell autophagy in vivo. Moreover, LCPAT1 knockdown in lung cancer cell lines resulted in decreased autophagy-associated gene expression and alleviated the cell autophagy induced by rapamycin.Conclusions: We speculate that LCPAT1 plays a crucial role in regulating autophagy in lung cancer.展开更多
●AIM:To observe the effect of inhibiting long non-coding RNA(lncRNA)metastasis-associated lung adenocarcinoma transcript 1(MALAT1)on diabetic neurodegeneration.●METHODS:Thirty-six 8-week-old C57 BL/6 mice were rando...●AIM:To observe the effect of inhibiting long non-coding RNA(lncRNA)metastasis-associated lung adenocarcinoma transcript 1(MALAT1)on diabetic neurodegeneration.●METHODS:Thirty-six 8-week-old C57 BL/6 mice were randomly divided into normal control,diabetic control,diabetic scrambled small interfering RNAs(siRNAs)and diabetic MALAT1-siRNA groups.After diabetic induction with streptozocin intraperitoneally-injection,the diabetic M A L AT 1-s i R N A g ro u p w a s i n t r av i t r e a l l y i n j e c te d with 1μL 20μmol/L MALAT1 siRNA,and the diabetic scrambled siRNA group was injected with the same amount of scrambled siRNA.Electroretinography was performed to examine photoreceptor functions 16 wk after diabetes induction.MALAT1 expression was detected via real time polymerase chain reaction.Cone morphological changes were examined using immunofluorescence.Rod morphological changes were examined by determining outer nuclear layer(ONL)thickness.●RESULTS:The upregulation of retinal MALAT1 expression was detected in the diabetic control mice,while MALAT1 expression in the diabetic MALAT1-siRNA mice was decreased by 91.48%compared to diabetic control mice.The diabetic MALAT1-siRNA and diabetic control mice showed lower a-wave and b-wave amplitudes than did the normal control mice in scotopic and photopic electroretinogram,while the diabetic MALAT1-siRNA mice showed higher amplitudes than diabetic control mice.Morphological examination revealed that ONL thickness in the diabetic MALAT1-siRNA and diabetic control mice was lower than normal control mice.However,ONL thickness was greater in the diabetic MALAT1-siRNA mice than diabetic control mice.Moreover,the diabetic control mice performed a sparser cone cell arrangement and shorter outer segment morphology than diabetic MALAT1-siRNA mice.●CONCLUSION:Inhibiting retinal MALAT1 results in mitigative effects on the retinal photoreceptors,thus alleviating diabetic neurodegeneration.展开更多
BACKGROUND The incidence of colon cancer(CC)is currently high,and is mainly treated with chemotherapy.Oxaliplatin(L-OHP)is a commonly used drug in chemotherapy;however,long-term use can induce drug resistance and seri...BACKGROUND The incidence of colon cancer(CC)is currently high,and is mainly treated with chemotherapy.Oxaliplatin(L-OHP)is a commonly used drug in chemotherapy;however,long-term use can induce drug resistance and seriously affect the prognosis of patients.Therefore,this study investigated the mechanism of Opainteracting protein 5 antisense RNA 1(OIP5-AS1)on L-OHP resistance by determining the expression of OIP5-AS1 and micro RNA-137(miR-137)in CC cells and the effects on L-OHP resistance,with the goal of identifying new targets for the treatment of CC.AIM To study the effects of long non-coding RNA OIP5-AS1 on L-OHP resistance in CC cell lines and its regulation of miR-137.METHODS A total of 114 CC patients admitted to China-Japan Union Hospital of Jilin University were enrolled,and the expression of miR-137 and OIP5-AS1 in tumor tissues and corresponding normal tumor-adjacent tissues was determined.The influence of OIP5-AS1 and miR-137 on the biological behavior of CC cells was evaluated.Resistance to L-OHP was induced in CC cells,and their activity was determined and evaluated using cell counting kit-8.Flow cytometry was used to analyze the apoptosis rate,Western blot to determine the levels of apoptosisrelated proteins,and dual luciferase reporter assay combined with RNA-binding protein immunoprecipitation to analyze the relationship between OIP5-AS1 and miR-137.RESULTS OIP5-AS1 was up-regulated in CC tissues and cells,while miR-137 was downregulated in CC tissues and cells.OIP5-AS1 was inversely correlated with miR-137(P<0.001).Silencing OIP5-AS1 expression significantly hindered the proliferation,invasion and migration abilities of CC cells and markedly increased the apoptosis rate.Up-regulation of miR-137 expression also suppressed these abilities in CC cells and increased the apoptosis rate.Moreover,silencing OIP5-AS1 and up-regulating miR-137 expression significantly intensified growth inhibition of drug-resistant CC cells and improved the sensitivity of CC cells to LOHP.OIP5-AS1 targetedly inhibited miR-137 expression,and silencing OIP5-AS1 reversed the resistance of CC cells to L-OHP by promoting the expression of miR-137.CONCLUSION Highly expressed in CC,OIP5-AS1 can affect the biological behavior of CC cells,and can also regulate the resistance of CC cells to L-OHP by mediating miR-137 expression.展开更多
BACKGROUND Previous studies have suggested that long non-coding RNAs(lncRNA)TP73-AS1 is significantly upregulated in several cancers.However,the biological role and clinical significance of TP73-AS1 in pancreatic canc...BACKGROUND Previous studies have suggested that long non-coding RNAs(lncRNA)TP73-AS1 is significantly upregulated in several cancers.However,the biological role and clinical significance of TP73-AS1 in pancreatic cancer(PC)remain unclear.AIM To investigate the role of TP73-AS1 in the growth and metastasis of PC.METHODS The expression of lncRNA TP73-AS1,miR-128-3p,and GOLM1 in PC tissues and cells was detected by quantitative real-time polymerase chain reaction.The bioinformatics prediction software ENCORI was used to predict the putative binding sites of miR-128-3p.The regulatory roles of TP73-AS1 and miR-128-3p in cell proliferation,migration,and invasion abilities were verified by Cell Counting Kit-8,wound-healing,and transwell assays,as well as flow cytometry and Western blot analysis.The interactions among TP73-AS1,miR-128-3p,and GOLM1 were explored by bioinformatics prediction,luciferase assay,and Western blot.RESULTS The expression of TP73-AS1 and miRNA-128-3p was dysregulated in PC tissues and cells.High TP73-AS1 expression was correlated with a poor prognosis.TP73-AS1 silencing inhibited PC cell proliferation,migration,and invasion in vitro as well as suppressed tumor growth in vivo.Mechanistically,TP73-AS1 was validated to promote PC progression through GOLM1 upregulation by competitively binding to miR-128-3p.CONCLUSION Our results demonstrated that TP73-AS1 promotes PC progression by regulating the miR-128-3p/GOLM1 axis,which might provide a potential treatment strategy for patients with PC.展开更多
Gastric cancer is one of the most common malignant gastrointestinal tumors whose morbidity and mortality account for the second and third place respectively in malignant tumors in China.As an important participant in ...Gastric cancer is one of the most common malignant gastrointestinal tumors whose morbidity and mortality account for the second and third place respectively in malignant tumors in China.As an important participant in tumor biology,the abnormal expression of long non-coding RNA(lncRNAs)in cancer cells is closely related to the occurrence and development of tumors and plays the role of oncogenes or tumor suppressor genes.In this study,we identified a novel lncRNA NFIA antisense RNA 1(NFIA-AS1)and explored its role and clinical significance in gastric cancer.Real-time quantitative PCR was performed to detect the expression of NFIA-AS1 in tumor tissues and corresponding normal tissues from 42 pairs of gastric cancer samples.The lower expression of NFIA-AS1 was significantly associated with larger tumor size,lower histological grade,and advanced TNM stage.Kaplan-meier analysis showed that NFIA-AS1 expression could be used as an independent predictor of overall survival.We also demonstrated that overexpression of NFIA-AS1 significantly inhibited the proliferation of gastric cancer cells through affecting p16 levels.In conclusion,our results suggest that the lncRNA NFIA-AS1 may play the role of tumor suppressor gene,and serve as a biomarker for prognosis or progression of gastric cancer.展开更多
Ovarian cancer(OC)is a major cause of cancer-related deaths among gynaecologicalmalignancies.Emerging studies suggest that the long non-coding RNA(lncRNA)may be the potential biomarker for the diagnosis and prognosis ...Ovarian cancer(OC)is a major cause of cancer-related deaths among gynaecologicalmalignancies.Emerging studies suggest that the long non-coding RNA(lncRNA)may be the potential biomarker for the diagnosis and prognosis of the cancer.The current study was carried out to investigate the role of lncRNA CCHE1 silencing in OC cell invasion and migration.Expression of lncRNA CCHE1 in normal ovarian cell Hose and OC cell lines HO 8910,A2780 and SKOV3 was detected.LncRNA were transfected with siRNA,and then the proliferation of cells was detected by using MTT assay.Cell invasion and migration was measured by using Transwell assay and scratch test,respectively.The protein levels of E-cadherin,N-cadherin,ERK,p38-MAPK and the phosphorylation of ERK and p38-MAPK in cells after siRNA transfection were detected by using Western blot analysis.Consequently,lncRNA CCHE1 expression was highly expressed in OC cell lines,especially in SKOV3 cells.siRNA1,siRNA2 and siRNA3 all decreased.lncRNA CCHE1 expression in SKOV3 cells and siRNA2 showed the best silencing efficacy.Silencing of lncRNA CCHE1 decreased proliferation,invasion and migration,and reduced the protein levels of N-cadherin,ERK,p38-MAPK and the phosphorylation of ERK and p38-MAPK,while reducing the protein level of E-cadherin in SKOV3 cells.Collectively,our study proved that the silencing of lncRNA CCHE1 could inhibit SKOV3 cell invasion and migration via inactivating the p38-MAPK signaling pathway.展开更多
Objective:To explore the interaction of long noncoding RNA (LncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) with microRNA (miRNA)-146a on the effect and mechanism of preeclampsia (PE) trophobla...Objective:To explore the interaction of long noncoding RNA (LncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) with microRNA (miRNA)-146a on the effect and mechanism of preeclampsia (PE) trophoblast function.Methods: Choriocarcinoma cell line JEG-3 were cultured in vitro, and JEG-3 cells were transfected into four groups, namely Control, sh-MALAT1, miR-146a-5p inhibitor and sh-MALATI+miR-146a-5p inhibitor group. The sh-MALAT1 group was transfected with sh-MALAT1, the miR-146a-5p inhibitor group was transfected with miR-146a-5p inhibitor, the sh-MALAT1+inhibitor group was co-transfected with sh-MALAT1 and miR-146a-5p inhibitor, and Isometric empty vector was added in to the Control group. The mRNA level was detected by qPCR;the target relationship between MALAT1 and miR-146a-5p was predicted by bioinformation;the proliferation ability of JEG-3 cells was detected by CCK8 experiment after the four groups of plasmids were transfected;Western blot was used to detect the expression of protein in JEG-3 cells after different treatments.Results: sh-MALATl significantly decreased sh-MALATl and increased the mRNA level of miR-146a-5p in the choriocarcinoma cell line JEG-3. sh-MALATl inhibited the proliferation of JEG-3 cells, miR-146a-5p inhibitor promoted the proliferation of JEG-3 cells and weakened the effect of sh-MALATl production. At the same time, sh-MALATl attenuates the expression of TRAF6, VEGR, and MMP2 proteins in trophoblast cells, while miR-146a-5p inhibitor can enhance its expression and reduce the inhibitory effect of sh-MALATl.Conclusion: MALATl and miR-146a can interact to affect the biological behavior of trophoblast cells in preeclampsia.展开更多
BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary...BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.展开更多
Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides mostly transcribed by RNA which do not encode proteins. Previously, lncRNAs were considered transcriptional byproducts called “junk DNA” wit...Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides mostly transcribed by RNA which do not encode proteins. Previously, lncRNAs were considered transcriptional byproducts called “junk DNA” with no biological functions. There are many studies conducted on lncRNAs showing they are actively involved in regulation of epigenetic, transcriptional, and post-transcriptional events. Expressions of lncRNAs are more different in many malignant tumors than in benign tumors and normal tissue. Aberration of lncRNAs is responsible to promote or suppress tumorigenesis and cancer progression. Under different circumstances, lncRNAs exhibit their roles in carcinogenesis such as MALAT1 is responsible for intervening mRNA instability, HOTAIR, MALAT1, ANRIL, PVT1 links with miRNA and histonemodifying complexes, MEG3 associates with miRNA, CCAT2, MEG3, GAS5, UCA1 allies with c-Myc or P53 causing suppression of tumor or oncogenesis. Abnormal expressions of lncRNAs are noticed in gynecological cancers, such as cervical cancer, ovarian cancer, and endometrial cancer. Identification of cervical cancer associated lncRNAs is necessary to understand the molecular biogenesis of cancers. In this review, we summarized the foundation and function of the lncRNAs in terms of tumor progression, invasion, prognosis, apoptosis, metastasis, and chemo-resistance. This review will provide references to determine the clinical applications of lncRNAs as ideal diagnostic biomarkers or therapeutic targets in cervical cancers.展开更多
Background:Drug resistance is the main factor contributing to cancer recurrence and poor prognosis.Exploration of drug resistance-related mechanisms and effective therapeutic targets are the aim of molecular targeted ...Background:Drug resistance is the main factor contributing to cancer recurrence and poor prognosis.Exploration of drug resistance-related mechanisms and effective therapeutic targets are the aim of molecular targeted therapy.In our study,the role of long non-coding RNA(lncRNA)AFAP1-AS1 in gemcitabine resistance and related mechanisms were explored in cervical cancer cells.Methods:Gemcitabine-resistant cervical cancer cell lines HT-3-Gem and SW756-Gem were constructed using the gemcitabine concentration gradient method.The overall survival rates and recurrence-free survival rates were evaluated by Kaplan-Meier analysis.The interaction was verified through a Dual-luciferase reporter gene assay and a Biotinylated RNA pull-down assay.Cell proliferation ability was assessed through methyl-thiazolyl-tetrazolium(MTT),soft agar,and colony formation experiments.Cell cycle and apoptosis were detected byflow cytometry.Results:Up-regulation of AFAP1-AS1 in cervical cancer predicted a poor prognosis.Besides,patients in the gemcitabine-resistance group had higher levels of AFAP1-AS1 than the gemcitabine-sensitive group.AFAP1-AS1 promoted tumor growth and induced gemcitabine tolerance of cervical cancer cells.In addition,AFAP1-AS1 mediated epidermal growth factor receptor(EGFR)expression by serving as a molecular sponge for microRNA-7a-5p(miR-7-5p).This present study also proved that the knockdown of EGFR or overexpression of miR-7a-5p abolished the accelerative role of AFAP1-AS1 overexpression in cancer progression and gemcitabine tolerance.Conclusions:In general,the AFAP1-AS1/miR-7-5p/EGFR axis was tightly related to the progression and gemcitabine tolerance of cervical cancer,providing potential targets for the management of cervical cancer.展开更多
Objective: Emerging evidence indicates that long non-coding RNAs(lnc RNAs) are critical in carcinogenesis and progression of ovarian cancer. This study aimed to explore the functions and molecular mechanisms of plasma...Objective: Emerging evidence indicates that long non-coding RNAs(lnc RNAs) are critical in carcinogenesis and progression of ovarian cancer. This study aimed to explore the functions and molecular mechanisms of plasmacytoma variant translocation I(PVT1) in ovarian cancer Methods: PVT1 and miR-214 were detected by qRT-PCR assays in ovarian cancer tissues and cells. The cell proliferation,migration, and invasion abilities were detected by cell functional experiments, respectively. Western blot assay was performed to detect epithelial-mesenchymal transition(EMT) markers. MiR-214 expression regulated by PVT1 was studied by RNA immunoprecipitation(RIP) and chromatin immunoprecipitation(Ch IP) assays.Results: The expression of PVT1 was up-regulated in ovarian cancer tissues and cell lines. Elevated PVT1 expression was associated with advanced stage and indicated poor prognosis for ovarian cancer patients. The knockdown of PVT1 impaired SKOV3 cell proliferation, migration, and invasion in vitro. The promotion of ovarian cancer progression by PVT1 involved in regulation of the epithelial-mesenchymal transition process and PVT1 interaction with EZH2 represses miR-214 expression in ovarian cancer cells.Conclusions: PVT1 plays an important role in ovarian cancer tumorigenesis, which might be as a novel diagnostic marker and therapeutic target for ovarian cancer.展开更多
LncRNA(long non-coding RNA) H19 is a transcript of the H19 gene that is expressed during embryogenesis.We previously discove red a role for circular lncRNA H19 in the onset and prognosis of cerebral ischemic stroke.In...LncRNA(long non-coding RNA) H19 is a transcript of the H19 gene that is expressed during embryogenesis.We previously discove red a role for circular lncRNA H19 in the onset and prognosis of cerebral ischemic stroke.In this study,we used serum from patients with ischemic stroke,and mouse and cell culture models to elucidate the roles of plasma and neuronal exosomes in the regulatory effect of lncRNA H19 on insulin-like growth factor-1 and its mechanism in ischemic stroke,using western blotting,quantitative real-time polymerase chain reaction,and enzyme-linked immunosorbent assays.Plasma exosomal IncRNA H19 was negatively associated with blood levels of insulin-like growth factor-1 in samples from patients with cerebral ischemic stroke.In a mouse model,levels of exosomal IncRNA H19 were positively correlated with plasma and cerebral lncRNA H19.In a cell co-culture model,we confirmed that IncRNA H19 was transported from neuro ns to astrocytes by exosomes to induce downregulation of insulin-like growth factor-1 through the H19/let-7 a/insulin-like growth factor-1 receptor axis.This study provides the first evidence for the transpo rtation of IncRNA H19 by exosomes and the relationship between IncRNA H19 and insulinlike growth factor-1.展开更多
基金supported by the Medical Science and Technology Research Foundation of Guangdong Province(No.A2020559).
文摘Objective This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1)in the development of hepatocellular carcinoma(HCC).Methods A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients.The interactions of PCED1B-AS1 and microRNA-34a(miR-34a)were detected by dual luciferase activity assay and RNA pull-down assay.The RNA expression levels of PCED1B-AS1,miR-34a and CD44 were detected by RT-qPCR,and the protein expression level of CD44 was determined by Western blotting.The cell proliferation was detected by cell proliferation assay,and the cell invasion and migration by transwell invasion assay.The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study.Results PCED1B-AS1 was highly expressed in HCC tissues,which was associated with poor survival of HCC patients.Furthermore,PCED1B-AS1 interacted with miR-34a in HCC cells,but they did not regulate the expression of each other.Additionally,PCED1B-AS1 increased the expression level of CD44,which was targeted by miR-34a.The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro,while CD44 exhibited the opposite effects.Furthermore,PCED1B-AS1 suppressed the role of miR-34a.Moreover,the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo.Conclusion PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.
基金Supported by the National Natural Science Foundation of China,No.82271628.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and aggressive tumor.Sorafenib is the first-line treatment for patients with advanced HCC,but resistance to sorafenib has become a significant challenge in this therapy.Cancer stem cells play a crucial role in sorafenib resistance in HCC.Our previous study revealed that the long non-coding RNA(lncRNA)KIF9-AS1 is an oncogenic gene in HCC.However,the role of KIF9-AS1 in drug resistance and cancer stemness in HCC remains unclear.Herein,we aimed to investigate the function and mechanism of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC.AIM To describe the role of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC and elucidate the underlying mechanism.METHODS Tumor tissue and adjacent non-cancerous tissue samples were collected from HCC patients.Sphere formation was quantified via a tumor sphere assay.Cell viability,proliferation,and apoptosis were evaluated via Cell Counting Kit-8,flow cytometry,and colony formation assays,respectively.The interactions between the lncRNA KIF9-AS1 and its downstream targets were confirmed via RNA immunoprecipitation and coimmunoprecipitation.The tumorigenic role of KIF9-AS1 was validated in a mouse model.RESULTS Compared with that in normal controls,the expression of the lncRNA KIF9-AS1 was upregulated in HCC tissues.Knockdown of KIF9-AS1 inhibited stemness and attenuated sorafenib resistance in HCC cells.Mechanistically,N6-methyladenosine modification mediated by methyltransferase-like 3/insulin-like growth factor 2 mRNA-binding protein 1 stabilized and increased the expression of KIF9-AS1.Additionally,KIF9-AS1 increased the stability and expression of short stature homeobox 2 by promoting ubiquitin-specific peptidase 1-induced deubiquitination.Furthermore,depletion of KIF9-AS1 alleviated sorafenib resistance in a xenograft mouse model of HCC.CONCLUSION The N6-methyladenosine-modified lncRNA KIF9-AS1 promoted stemness and sorafenib resistance in HCC by upregulating short stature homeobox 2 expression.
基金Natural Science Foundation of Shandong Province,No.ZR2020MH207 and No.ZR2020MH251.
文摘BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.
文摘BACKGROUND： The majority of mammalian genomes have been found to be transcribed into non-coding RNAs. One category of non-coding RNAs is classified as long non-coding RNAs （lncRNAs） based on their transcript sizes larger than 200 nucleotides. Growing evidence has shown that lncRNAs are not junk transcripts and play regulatory roles in multiple aspects of biological processes. Dysregulation of lncRNA expression has also been linked to diseases, in particular cancer. Therefore, studies of lncRNAs have attracted significant interest in the field of medical research. Nuclear enriched abundant transcript 1 （NEAT1）, a nuclear lncRNA, has recently emerged as a key regulator involved in various cellular processes, physiological responses, developmental processes, and disease development and progression. OBJECTIVE： This review will summarize and discuss the most recent findings with regard to the roles of NEAT1 in the function of the nuclear paraspeckle, cellular pathways, and physiological responses and processes. Particularly, the most recently reported studies regarding the pathological roles of deregulated NEAT1 in cancer are highlighted in this review. METHODS： We performed a systematic literature search using the Pubmed search engine. Studies published over the past 8 years （between January 2009 and August 2016） were the sources of literature review. The following keywords were used： ＂Nuclear enriched abundant transcript 1,＂ ＂NEATI,＂ and ＂paraspeckles.＂ RESULTS： The Pubmed search identified 34 articles related to the topic of the review. Among the identified literature, 13 articles report findings related to cellular functions of NEAT1 and eight articles are the investigations of physiological functions of NEAT1. The remaining 13 articles are studies of the roles of NEAT1 in cancers. CONCLUSION： Recent advances in NEAT1 studies reveal the multifimctional roles of NEAT1 in various biological processes, which are beyond its role in nuclear paraspeckles. Recent studies also indicate that dysregulation of NEAT1 function contributes to the development and progression of various cancers. More investigations will be needed to address the detailed mechanisms regarding how NEAT1 executes its cellular and physiological functions and how NEAT1 dysregulation results in tumorigenesis, and to explore the potential of NEAT1 as a target in cancer diagnosis, prognosis and therapy.
基金This work was supported in part by National Natural Science Foundation Grants of China(81530003)China Postdoctoral Science Foundation(2017M611580).
文摘Changes in the abundance and activity of long non-coding RNAs(lncRNAs)have an important impact on the development of cancer.The nuclear paraspeckle assembly transcript 1(NEAT1)has been reported to be overexpressed in many types of cancer since its discovery.However,inconsistencies exist as NEAT1 can also function as a tumor suppressor in certain types of cancer,such as acute promyelocytic leukemia.Here we systematically describe our current understanding of NEAT1 in tumor initiation and progression.First,we analyzed the expression patterns of NEAT1 in various normal tissues and malignant cancers using data from public data portals,the Genotype-Tissue Expression Project(GTEx)and the Cancer Genome Atlas(TCGA),together with recent progress in the study of NEAT1 in various types of cancer.Second,we discussed the functions and mechanisms of NEAT1 in modulating tumor activity.Then,the upstream transcription factors and downstream microRNA targets of NEAT1 in the transcription cascade of cancers were also summarized.These data highlight the emerging role of NEAT1 in tumorigenesis,and present promising targetable pathways and clinical opportunities for tumor prevention and classifications.
文摘Non-alcoholic fatty liver disease(NAFLD)is emerging as a common cause of chronic liver disease in children and adults.NAFLD can progress to steatohepa-titis and potentially even hepatocellular carcinoma.Early identification of pati-ents at risk for progressive disease is crucial for managing NAFLD.Recent studies have identified long noncoding RNAs(lncRNAs),circular RNAs,and microRNAs as playing important roles in the pathogenesis of NAFLD.These noncoding RNAs are involved in modulating several metabolic pathways such as hepatic glucose and lipid metabolism,oxidative stress,and even carcinogenesis.Elevated levels of lncARSR and lncRNA nuclear-enriched abundant transcript 1 have been found in patients with NAFLD.In addition,lncRNAs such as PRYP4-3 and RP11-128N14.5 can distinguish patients with NAFLD from healthy indi-viduals.Increased MEG3 expression has been observed in both NAFLD and non-alcoholic steatohepatitis,suggesting that it may help predict patients at risk for disease progression.With advances in transcriptomics,we may discover additional targets to help in the identification and prognostication of NAFLD.
文摘BACKGROUND Esophageal cancer is a common digestive tract tumor that is generally treated with radiotherapy.Poor responses to radiotherapy in most patients generally result in local radiotherapy failure,so it is essential to find new radiosensitizers that can enhance the response of cancer cells to radiotherapy and improve the survival of esophageal cancer patients with radiation resistance.The long noncoding RNA(lncRNA)Rpph1 is highly expressed in human gastric cancer tissues,and represses breast cancer cell proliferation and tumorigenesis.However,the expression of lncRNA Rpph1 in esophageal cancer and its relationship with radio-sensitivity has not been studied.AIM To explore the value of lncRNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy.METHODS Eighty-three patients with esophageal cancer admitted to Qilu Hospital of Shandong University and 90 healthy participants who received physical examinations were collected as research participants.The expression of Rpph1 was determined by qRT-PCR.siRNA-NC and siRNA-Rpph1 were transfected into esophageal cancer cell lines,and cells without transfection were designated as the blank control group.Cell survival was tested by colony formation assays,and the levels of proteins related to apoptosis and epithelial-mesenchymal transitions were determined by Western blot assays.Cell proliferation was assessed by MTT assays,cell apoptosis by flow cytometry,and cell migration by wound-healing assays.Changes in cell cycle distribution were monitored.RESULTS Rpph1 was highly expressed in esophageal carcinoma,making it a promising marker for the diagnosis of esophageal cancer.Rpph1 could also be used to distinguish different short-term responses,T stages,N stages,and clinical stages of esophageal cancer patients.The results of 3-year overall survival favored patients with lower Rpph1 expression over patients with higher Rpph1 expression(P<0.05).In vitro and in vivo experiments showed that silencing Rpph1 expression led to higher sensitivity of esophageal cancer cells to radiotherapy,stronger apoptosis in esophageal cancer cells induced by radiotherapy,higher expression of Bax and caspase-3,and lower expression of Bcl-2(Bax,caspase-3,and Bcl-2 are apoptosis-related proteins).Additionally,silencing Rpph1 attenuated radiation-induced G2/M phase arrest,and significantly inhibited the expression of proteins involved in cell proliferation,migration,and epithelial-mesenchymal transition regulation in esophageal cancer cells.CONCLUSION Rpph1 is highly expressed in esophageal cancer.Silencing Rpph1 expression can promote cell apoptosis,inhibit cell proliferation and migration,and increase radio-sensitivity.
基金funded by the National Natural Science Foundation of China (Grant No. 81401046 and No.21777099)Shanghai Jiao Tong University Interdisciplinary Research Key Grant (Grant No. YG2015ZD01)Shanghai Jiao Tong University "New Young Teachers Startup Plan"
文摘Objective: Long non-coding RNAs(lnc RNAs) are involved in numerous biological processes in lung cancer cells. In our previous studies, we identified a lnc RNA, ENST00000439577, which is highly expressed in lung carcinomas, and termed it lung cancer progression-associated transcript 1(LCPAT1). To characterize the role of LCPAT1 in lung cancer, we conducted the current study.Methods: Expression of LCPAT1 and autophagy-associated markers in tumor tissues and lung cancer cell lines was determined by real-time quantitative polymerase chain reaction(q PCR). Hematoxylin and eosin(HE) staining, q PCR, Western blot, and immunohistochemistry were performed to evaluate xenografted tumor tissues. Autophagy induced by rapamycin was detected by Western blot and immunofluorescence in lung cancer cell lines.Results: Expression of LCPAT1 and microtubule-associated protein 1 light chain 3 beta(LC3B) was positively correlated in lung cancer. Knockdown of LCPAT1 inhibited tumor growth and suppressed cell autophagy in vivo. Moreover, LCPAT1 knockdown in lung cancer cell lines resulted in decreased autophagy-associated gene expression and alleviated the cell autophagy induced by rapamycin.Conclusions: We speculate that LCPAT1 plays a crucial role in regulating autophagy in lung cancer.
基金Supported by National Natural Science Foundation of China(No.81960158,No.81760176)Key Scientific research Program of Jiangxi Education Department(No.GJJ190003).
文摘●AIM:To observe the effect of inhibiting long non-coding RNA(lncRNA)metastasis-associated lung adenocarcinoma transcript 1(MALAT1)on diabetic neurodegeneration.●METHODS:Thirty-six 8-week-old C57 BL/6 mice were randomly divided into normal control,diabetic control,diabetic scrambled small interfering RNAs(siRNAs)and diabetic MALAT1-siRNA groups.After diabetic induction with streptozocin intraperitoneally-injection,the diabetic M A L AT 1-s i R N A g ro u p w a s i n t r av i t r e a l l y i n j e c te d with 1μL 20μmol/L MALAT1 siRNA,and the diabetic scrambled siRNA group was injected with the same amount of scrambled siRNA.Electroretinography was performed to examine photoreceptor functions 16 wk after diabetes induction.MALAT1 expression was detected via real time polymerase chain reaction.Cone morphological changes were examined using immunofluorescence.Rod morphological changes were examined by determining outer nuclear layer(ONL)thickness.●RESULTS:The upregulation of retinal MALAT1 expression was detected in the diabetic control mice,while MALAT1 expression in the diabetic MALAT1-siRNA mice was decreased by 91.48%compared to diabetic control mice.The diabetic MALAT1-siRNA and diabetic control mice showed lower a-wave and b-wave amplitudes than did the normal control mice in scotopic and photopic electroretinogram,while the diabetic MALAT1-siRNA mice showed higher amplitudes than diabetic control mice.Morphological examination revealed that ONL thickness in the diabetic MALAT1-siRNA and diabetic control mice was lower than normal control mice.However,ONL thickness was greater in the diabetic MALAT1-siRNA mice than diabetic control mice.Moreover,the diabetic control mice performed a sparser cone cell arrangement and shorter outer segment morphology than diabetic MALAT1-siRNA mice.●CONCLUSION:Inhibiting retinal MALAT1 results in mitigative effects on the retinal photoreceptors,thus alleviating diabetic neurodegeneration.
文摘BACKGROUND The incidence of colon cancer(CC)is currently high,and is mainly treated with chemotherapy.Oxaliplatin(L-OHP)is a commonly used drug in chemotherapy;however,long-term use can induce drug resistance and seriously affect the prognosis of patients.Therefore,this study investigated the mechanism of Opainteracting protein 5 antisense RNA 1(OIP5-AS1)on L-OHP resistance by determining the expression of OIP5-AS1 and micro RNA-137(miR-137)in CC cells and the effects on L-OHP resistance,with the goal of identifying new targets for the treatment of CC.AIM To study the effects of long non-coding RNA OIP5-AS1 on L-OHP resistance in CC cell lines and its regulation of miR-137.METHODS A total of 114 CC patients admitted to China-Japan Union Hospital of Jilin University were enrolled,and the expression of miR-137 and OIP5-AS1 in tumor tissues and corresponding normal tumor-adjacent tissues was determined.The influence of OIP5-AS1 and miR-137 on the biological behavior of CC cells was evaluated.Resistance to L-OHP was induced in CC cells,and their activity was determined and evaluated using cell counting kit-8.Flow cytometry was used to analyze the apoptosis rate,Western blot to determine the levels of apoptosisrelated proteins,and dual luciferase reporter assay combined with RNA-binding protein immunoprecipitation to analyze the relationship between OIP5-AS1 and miR-137.RESULTS OIP5-AS1 was up-regulated in CC tissues and cells,while miR-137 was downregulated in CC tissues and cells.OIP5-AS1 was inversely correlated with miR-137(P<0.001).Silencing OIP5-AS1 expression significantly hindered the proliferation,invasion and migration abilities of CC cells and markedly increased the apoptosis rate.Up-regulation of miR-137 expression also suppressed these abilities in CC cells and increased the apoptosis rate.Moreover,silencing OIP5-AS1 and up-regulating miR-137 expression significantly intensified growth inhibition of drug-resistant CC cells and improved the sensitivity of CC cells to LOHP.OIP5-AS1 targetedly inhibited miR-137 expression,and silencing OIP5-AS1 reversed the resistance of CC cells to L-OHP by promoting the expression of miR-137.CONCLUSION Highly expressed in CC,OIP5-AS1 can affect the biological behavior of CC cells,and can also regulate the resistance of CC cells to L-OHP by mediating miR-137 expression.
基金National Natural Science Foundation of China,No.81974372.
文摘BACKGROUND Previous studies have suggested that long non-coding RNAs(lncRNA)TP73-AS1 is significantly upregulated in several cancers.However,the biological role and clinical significance of TP73-AS1 in pancreatic cancer(PC)remain unclear.AIM To investigate the role of TP73-AS1 in the growth and metastasis of PC.METHODS The expression of lncRNA TP73-AS1,miR-128-3p,and GOLM1 in PC tissues and cells was detected by quantitative real-time polymerase chain reaction.The bioinformatics prediction software ENCORI was used to predict the putative binding sites of miR-128-3p.The regulatory roles of TP73-AS1 and miR-128-3p in cell proliferation,migration,and invasion abilities were verified by Cell Counting Kit-8,wound-healing,and transwell assays,as well as flow cytometry and Western blot analysis.The interactions among TP73-AS1,miR-128-3p,and GOLM1 were explored by bioinformatics prediction,luciferase assay,and Western blot.RESULTS The expression of TP73-AS1 and miRNA-128-3p was dysregulated in PC tissues and cells.High TP73-AS1 expression was correlated with a poor prognosis.TP73-AS1 silencing inhibited PC cell proliferation,migration,and invasion in vitro as well as suppressed tumor growth in vivo.Mechanistically,TP73-AS1 was validated to promote PC progression through GOLM1 upregulation by competitively binding to miR-128-3p.CONCLUSION Our results demonstrated that TP73-AS1 promotes PC progression by regulating the miR-128-3p/GOLM1 axis,which might provide a potential treatment strategy for patients with PC.
基金supported by grants from the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX17_1301 to E.Z.)the National Natural Science Foundation of China (81730066 to D.M.).
文摘Gastric cancer is one of the most common malignant gastrointestinal tumors whose morbidity and mortality account for the second and third place respectively in malignant tumors in China.As an important participant in tumor biology,the abnormal expression of long non-coding RNA(lncRNAs)in cancer cells is closely related to the occurrence and development of tumors and plays the role of oncogenes or tumor suppressor genes.In this study,we identified a novel lncRNA NFIA antisense RNA 1(NFIA-AS1)and explored its role and clinical significance in gastric cancer.Real-time quantitative PCR was performed to detect the expression of NFIA-AS1 in tumor tissues and corresponding normal tissues from 42 pairs of gastric cancer samples.The lower expression of NFIA-AS1 was significantly associated with larger tumor size,lower histological grade,and advanced TNM stage.Kaplan-meier analysis showed that NFIA-AS1 expression could be used as an independent predictor of overall survival.We also demonstrated that overexpression of NFIA-AS1 significantly inhibited the proliferation of gastric cancer cells through affecting p16 levels.In conclusion,our results suggest that the lncRNA NFIA-AS1 may play the role of tumor suppressor gene,and serve as a biomarker for prognosis or progression of gastric cancer.
文摘Ovarian cancer(OC)is a major cause of cancer-related deaths among gynaecologicalmalignancies.Emerging studies suggest that the long non-coding RNA(lncRNA)may be the potential biomarker for the diagnosis and prognosis of the cancer.The current study was carried out to investigate the role of lncRNA CCHE1 silencing in OC cell invasion and migration.Expression of lncRNA CCHE1 in normal ovarian cell Hose and OC cell lines HO 8910,A2780 and SKOV3 was detected.LncRNA were transfected with siRNA,and then the proliferation of cells was detected by using MTT assay.Cell invasion and migration was measured by using Transwell assay and scratch test,respectively.The protein levels of E-cadherin,N-cadherin,ERK,p38-MAPK and the phosphorylation of ERK and p38-MAPK in cells after siRNA transfection were detected by using Western blot analysis.Consequently,lncRNA CCHE1 expression was highly expressed in OC cell lines,especially in SKOV3 cells.siRNA1,siRNA2 and siRNA3 all decreased.lncRNA CCHE1 expression in SKOV3 cells and siRNA2 showed the best silencing efficacy.Silencing of lncRNA CCHE1 decreased proliferation,invasion and migration,and reduced the protein levels of N-cadherin,ERK,p38-MAPK and the phosphorylation of ERK and p38-MAPK,while reducing the protein level of E-cadherin in SKOV3 cells.Collectively,our study proved that the silencing of lncRNA CCHE1 could inhibit SKOV3 cell invasion and migration via inactivating the p38-MAPK signaling pathway.
基金General Project of Hainan Natural Science Foundation(818MS123)The scientific research project of Hainan University(Hnky2019-40)
文摘Objective:To explore the interaction of long noncoding RNA (LncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) with microRNA (miRNA)-146a on the effect and mechanism of preeclampsia (PE) trophoblast function.Methods: Choriocarcinoma cell line JEG-3 were cultured in vitro, and JEG-3 cells were transfected into four groups, namely Control, sh-MALAT1, miR-146a-5p inhibitor and sh-MALATI+miR-146a-5p inhibitor group. The sh-MALAT1 group was transfected with sh-MALAT1, the miR-146a-5p inhibitor group was transfected with miR-146a-5p inhibitor, the sh-MALAT1+inhibitor group was co-transfected with sh-MALAT1 and miR-146a-5p inhibitor, and Isometric empty vector was added in to the Control group. The mRNA level was detected by qPCR;the target relationship between MALAT1 and miR-146a-5p was predicted by bioinformation;the proliferation ability of JEG-3 cells was detected by CCK8 experiment after the four groups of plasmids were transfected;Western blot was used to detect the expression of protein in JEG-3 cells after different treatments.Results: sh-MALATl significantly decreased sh-MALATl and increased the mRNA level of miR-146a-5p in the choriocarcinoma cell line JEG-3. sh-MALATl inhibited the proliferation of JEG-3 cells, miR-146a-5p inhibitor promoted the proliferation of JEG-3 cells and weakened the effect of sh-MALATl production. At the same time, sh-MALATl attenuates the expression of TRAF6, VEGR, and MMP2 proteins in trophoblast cells, while miR-146a-5p inhibitor can enhance its expression and reduce the inhibitory effect of sh-MALATl.Conclusion: MALATl and miR-146a can interact to affect the biological behavior of trophoblast cells in preeclampsia.
基金Supported by Innovative Team of Jiangsu Province,No.CXTDA2017042Jiangsu Provincial Medical Youth Talent,No.QNRC2016508In-Hospital Project of Taizhou People's Hospital,No.ZL201930.
文摘BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.
文摘Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides mostly transcribed by RNA which do not encode proteins. Previously, lncRNAs were considered transcriptional byproducts called “junk DNA” with no biological functions. There are many studies conducted on lncRNAs showing they are actively involved in regulation of epigenetic, transcriptional, and post-transcriptional events. Expressions of lncRNAs are more different in many malignant tumors than in benign tumors and normal tissue. Aberration of lncRNAs is responsible to promote or suppress tumorigenesis and cancer progression. Under different circumstances, lncRNAs exhibit their roles in carcinogenesis such as MALAT1 is responsible for intervening mRNA instability, HOTAIR, MALAT1, ANRIL, PVT1 links with miRNA and histonemodifying complexes, MEG3 associates with miRNA, CCAT2, MEG3, GAS5, UCA1 allies with c-Myc or P53 causing suppression of tumor or oncogenesis. Abnormal expressions of lncRNAs are noticed in gynecological cancers, such as cervical cancer, ovarian cancer, and endometrial cancer. Identification of cervical cancer associated lncRNAs is necessary to understand the molecular biogenesis of cancers. In this review, we summarized the foundation and function of the lncRNAs in terms of tumor progression, invasion, prognosis, apoptosis, metastasis, and chemo-resistance. This review will provide references to determine the clinical applications of lncRNAs as ideal diagnostic biomarkers or therapeutic targets in cervical cancers.
文摘Background:Drug resistance is the main factor contributing to cancer recurrence and poor prognosis.Exploration of drug resistance-related mechanisms and effective therapeutic targets are the aim of molecular targeted therapy.In our study,the role of long non-coding RNA(lncRNA)AFAP1-AS1 in gemcitabine resistance and related mechanisms were explored in cervical cancer cells.Methods:Gemcitabine-resistant cervical cancer cell lines HT-3-Gem and SW756-Gem were constructed using the gemcitabine concentration gradient method.The overall survival rates and recurrence-free survival rates were evaluated by Kaplan-Meier analysis.The interaction was verified through a Dual-luciferase reporter gene assay and a Biotinylated RNA pull-down assay.Cell proliferation ability was assessed through methyl-thiazolyl-tetrazolium(MTT),soft agar,and colony formation experiments.Cell cycle and apoptosis were detected byflow cytometry.Results:Up-regulation of AFAP1-AS1 in cervical cancer predicted a poor prognosis.Besides,patients in the gemcitabine-resistance group had higher levels of AFAP1-AS1 than the gemcitabine-sensitive group.AFAP1-AS1 promoted tumor growth and induced gemcitabine tolerance of cervical cancer cells.In addition,AFAP1-AS1 mediated epidermal growth factor receptor(EGFR)expression by serving as a molecular sponge for microRNA-7a-5p(miR-7-5p).This present study also proved that the knockdown of EGFR or overexpression of miR-7a-5p abolished the accelerative role of AFAP1-AS1 overexpression in cancer progression and gemcitabine tolerance.Conclusions:In general,the AFAP1-AS1/miR-7-5p/EGFR axis was tightly related to the progression and gemcitabine tolerance of cervical cancer,providing potential targets for the management of cervical cancer.
文摘Objective: Emerging evidence indicates that long non-coding RNAs(lnc RNAs) are critical in carcinogenesis and progression of ovarian cancer. This study aimed to explore the functions and molecular mechanisms of plasmacytoma variant translocation I(PVT1) in ovarian cancer Methods: PVT1 and miR-214 were detected by qRT-PCR assays in ovarian cancer tissues and cells. The cell proliferation,migration, and invasion abilities were detected by cell functional experiments, respectively. Western blot assay was performed to detect epithelial-mesenchymal transition(EMT) markers. MiR-214 expression regulated by PVT1 was studied by RNA immunoprecipitation(RIP) and chromatin immunoprecipitation(Ch IP) assays.Results: The expression of PVT1 was up-regulated in ovarian cancer tissues and cell lines. Elevated PVT1 expression was associated with advanced stage and indicated poor prognosis for ovarian cancer patients. The knockdown of PVT1 impaired SKOV3 cell proliferation, migration, and invasion in vitro. The promotion of ovarian cancer progression by PVT1 involved in regulation of the epithelial-mesenchymal transition process and PVT1 interaction with EZH2 represses miR-214 expression in ovarian cancer cells.Conclusions: PVT1 plays an important role in ovarian cancer tumorigenesis, which might be as a novel diagnostic marker and therapeutic target for ovarian cancer.
基金supported by the National Natural Science Foundation of China,No.82271353(to JW)Key Research and Development Program of Liaoning Province,No.2020JH2/10300047(to JF).
文摘LncRNA(long non-coding RNA) H19 is a transcript of the H19 gene that is expressed during embryogenesis.We previously discove red a role for circular lncRNA H19 in the onset and prognosis of cerebral ischemic stroke.In this study,we used serum from patients with ischemic stroke,and mouse and cell culture models to elucidate the roles of plasma and neuronal exosomes in the regulatory effect of lncRNA H19 on insulin-like growth factor-1 and its mechanism in ischemic stroke,using western blotting,quantitative real-time polymerase chain reaction,and enzyme-linked immunosorbent assays.Plasma exosomal IncRNA H19 was negatively associated with blood levels of insulin-like growth factor-1 in samples from patients with cerebral ischemic stroke.In a mouse model,levels of exosomal IncRNA H19 were positively correlated with plasma and cerebral lncRNA H19.In a cell co-culture model,we confirmed that IncRNA H19 was transported from neuro ns to astrocytes by exosomes to induce downregulation of insulin-like growth factor-1 through the H19/let-7 a/insulin-like growth factor-1 receptor axis.This study provides the first evidence for the transpo rtation of IncRNA H19 by exosomes and the relationship between IncRNA H19 and insulinlike growth factor-1.
