Previous study revealed that ferritin heavy chain-1(FTH1)could regulate ferritinophagy and affect intracellular Fe^(+)content in various tumors,while its N6-methyladenosine(m6A)RNA methylation was closely related the ...Previous study revealed that ferritin heavy chain-1(FTH1)could regulate ferritinophagy and affect intracellular Fe^(+)content in various tumors,while its N6-methyladenosine(m6A)RNA methylation was closely related the prognosis of ovarian cancer patients.However,little is known about the role of FTH1 m6A methylation in ovarian cancer(OC)and its possible action mechanisms.In this study we constructed FTH1 m6A methylation regulatory pathway(LncRNA CACNA1G-AS1/IGF2BP1)according to related bioinformatics analysis and research,through clinical sample detections we found that these pathway regulatory factors were significantly up-regulated in ovarian cancer tissues,and their expression levels were closely related to the malignant phenotype of ovarian cancer.In vitro cell experiments showed that LncRNA CACNA1G-AS1 could up-regulate FTH1 expression through IGF2BP1 axis,thus inhibited ferroptosis by regulating ferritinophagy,and finally promoted proliferation and migration in ovarian cancer cells.Tumor-bearing mice studies showed that the knock-down of LncRNA CACNA1G-AS1 could inhibited the tumorigenesis of ovarian cancer cells in vivo condition.Our results demonstrated that LncRNA CACNA1G-AS1 could promote the malignant phenotypes of ovarian cancer cells through FTH1-IGF2BP1 regulated ferroptosis.展开更多
Objective: Hepatocellular carcinoma (HCC) is still one of the most common death-related malignancies worldwide. Because the way onset and progression are hidden most, HCC diagnoses are made at an advanced stage, wh...Objective: Hepatocellular carcinoma (HCC) is still one of the most common death-related malignancies worldwide. Because the way onset and progression are hidden most, HCC diagnoses are made at an advanced stage, when they are unsuitable for surgical resection. MicroRNAs are a class of small non-coding RNAs, participating in many aspects of cancers. In this study, we tried to establish the role of micreRNA-718 (miR-718) in the malignant phenotype of HCC cells and its possible role in HCC diagnosis. Methods: Here we first used a methylthiazolyldiphenyl- tetrazolium bromide (MTT) assay, Transwell migration and invasion assays, and colony formation assay to evaluate the impact of miR-718 on the malignant phenotypes of HCC cells. Then, we used bioinformatic methods to predict the target gene of miR-718 and used green fluorescence protein (GFP) reporter assay, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) to validate the regulation relationship. Finally, we determined the role of the target gene in the HCC phenotype. Results: We found that the expression of miR-718 was significantly reduced in various HCC cell lines and HCC tissues. Re-expression of miR-718 significantly reduced the cellular viability and colony formation ability as well as inhibited the migration and invasion abilities of HCC cell lines. Early growth response protein 3 (EGR3) is a direct target of miR-718 and is negatively regulated by miR-718. EGR3 could increase the via- bility and proliferation of HCC cells, and promot the migration and invasion of HCC cells. Conclusions: miR-718 acts as a tumor suppressive microRNA in HCC via regulating the expression of EGR3, which may provide a new diagnostic 07) found that overexpreget for HCC.展开更多
Objective To explore the expression of etheràgo-go1(Eag1)in human osteosarcoma and its molecular mechanisms of regulating the malignant phenotype of osteosarcoma.Methods The expression levels of Eag1 in osteosarc...Objective To explore the expression of etheràgo-go1(Eag1)in human osteosarcoma and its molecular mechanisms of regulating the malignant phenotype of osteosarcoma.Methods The expression levels of Eag1 in osteosarcoma cell lines and human osteosarcoma tissues were detected by reverse transcription polymerase chain reaction(RT-PCR),western blot analysis and immunohistochemistry.The small interfering RNA(siRNA)was展开更多
Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective treatment.In this investigation,we explored the functional interaction of miR-30a...Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective treatment.In this investigation,we explored the functional interaction of miR-30a-5p and the putative transcription factor 2 of the homeodomain(PHTF2)in dictating the aggressiveness and metastasis of lung adenocarcinoma.Method:We collected clinical samples to evaluate the expression patterns of miR-30a-5p and PHTF2 in lung adenocarcinoma along with normal tissues.Cellular experiments including cell count kit(CCK)-8 growth assay,apoptosis analysis,migration and invasion examinations were performed to assess the aggressiveness of lung adenocarcinoma cells.Furthermore,we examined tumorigenesis and metastasis in a nude mouse model.Results:MiR-30a-5p exhibited downregulation pattern in lung adenocarcinoma samples.Transfection of miR-30a-5p mimic in lung adenocarcinoma cells resulted in the suppression of malignant characteristics.Notably,the administration of miR-30a-5p mimic also curbed tumorigenesis and metastasis of lung adenocarcinoma cells in animal model.Moreover,PHTF2 was found to be a molecular target of miR-30a-5p.Upregulating PHTF2 counteracted the tumor-suppressive effect of the miR-30a-5p mimic.Conclusion:miR-30a-5p functions as a tumor-suppressive molecule while PHTF2 acts as an oncogenic factor in the development and metastasis of lung adenocarcinoma.Therefore,targeting miR-30a-5p and PHTF2 could be developed into a promising therapeutic approach for inhibiting metastasis in lung adenocarcinoma.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal neoplasms of the gastrointestinal tract.Surgical resection and tyrosine kinase inhibitors are defined as the main treatments but cannot ...BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal neoplasms of the gastrointestinal tract.Surgical resection and tyrosine kinase inhibitors are defined as the main treatments but cannot cure patients with advanced GIST,which eventually develops into recurrence and acquired drug resistance.Therefore,it is necessary to identify prognostic biomarkers and new therapeutic targets for GISTs.CC chemokine receptor type 8(CCR8)protein participates in regulation of immune responses.Recent studies on CCR8 in nonsmall cell lung cancer and colorectal cancer showed that it was highly expressed in tumor-infiltrating regulatory T cells and correlated with a poor prognosis.AIM To detect CCR8 expression in GIST tissues and analyze its relationships with clinicopathological features and prognosis in patients with GISTs.METHODS Tissue samples were used for the tissue microarrays construction.The microarrays were then subjected to immunohistochemical analyses to detect CCR8 expression.Next,Kaplan–Meier analysis was utilized to calculate the survival rate of patients with complete follow-up data,and the potential prognostic value of CCR8 was evaluated by Cox regression analysis.Finally,a Gene Ontology/Kyoto Encyclopedia of Genes and Genomes single-gene enrichment chart of CCR8 was constructed using the STRING database.RESULTS CCR8-positive signals were detected as brown or brown-yellow particles by immunohistochemistry located in the cytoplasm.Among 125 tissue samples,74 had CCR8 high expression and 51 had low or negative expression.Statistical analyses suggested CCR8 was significantly correlated with tumor size,mitotic index,AFIP-Miettinen risk classification and tumor location.Kaplan–Meier and multivariate analyses showed that patients with low or negative CCR8 expression,mitotic index<5/high-power fields(HPF)and tumor diameter<5 cm had a better prognosis.Based on the STRING database,CCR8 was significantly enriched in biological processes such as tumor immunity,T lymphocyte chemotaxis,migration and pathways like the nuclear factor-κB and tumor necrosis factor pathways as well as intestinal immune regulation networks.CONCLUSION CCR8 is a prognostic biomarker for malignant potential of GISTs,with high expression correlated with malignancy and poor prognosis.展开更多
基金Suzhou Youth Project of Promoting Health through Science and Education,Grant ID:KJXW2022010.
文摘Previous study revealed that ferritin heavy chain-1(FTH1)could regulate ferritinophagy and affect intracellular Fe^(+)content in various tumors,while its N6-methyladenosine(m6A)RNA methylation was closely related the prognosis of ovarian cancer patients.However,little is known about the role of FTH1 m6A methylation in ovarian cancer(OC)and its possible action mechanisms.In this study we constructed FTH1 m6A methylation regulatory pathway(LncRNA CACNA1G-AS1/IGF2BP1)according to related bioinformatics analysis and research,through clinical sample detections we found that these pathway regulatory factors were significantly up-regulated in ovarian cancer tissues,and their expression levels were closely related to the malignant phenotype of ovarian cancer.In vitro cell experiments showed that LncRNA CACNA1G-AS1 could up-regulate FTH1 expression through IGF2BP1 axis,thus inhibited ferroptosis by regulating ferritinophagy,and finally promoted proliferation and migration in ovarian cancer cells.Tumor-bearing mice studies showed that the knock-down of LncRNA CACNA1G-AS1 could inhibited the tumorigenesis of ovarian cancer cells in vivo condition.Our results demonstrated that LncRNA CACNA1G-AS1 could promote the malignant phenotypes of ovarian cancer cells through FTH1-IGF2BP1 regulated ferroptosis.
基金Project supported by the Science and Technology Project of Higher Education of Shandong Province(No.J12LK07),China
文摘Objective: Hepatocellular carcinoma (HCC) is still one of the most common death-related malignancies worldwide. Because the way onset and progression are hidden most, HCC diagnoses are made at an advanced stage, when they are unsuitable for surgical resection. MicroRNAs are a class of small non-coding RNAs, participating in many aspects of cancers. In this study, we tried to establish the role of micreRNA-718 (miR-718) in the malignant phenotype of HCC cells and its possible role in HCC diagnosis. Methods: Here we first used a methylthiazolyldiphenyl- tetrazolium bromide (MTT) assay, Transwell migration and invasion assays, and colony formation assay to evaluate the impact of miR-718 on the malignant phenotypes of HCC cells. Then, we used bioinformatic methods to predict the target gene of miR-718 and used green fluorescence protein (GFP) reporter assay, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) to validate the regulation relationship. Finally, we determined the role of the target gene in the HCC phenotype. Results: We found that the expression of miR-718 was significantly reduced in various HCC cell lines and HCC tissues. Re-expression of miR-718 significantly reduced the cellular viability and colony formation ability as well as inhibited the migration and invasion abilities of HCC cell lines. Early growth response protein 3 (EGR3) is a direct target of miR-718 and is negatively regulated by miR-718. EGR3 could increase the via- bility and proliferation of HCC cells, and promot the migration and invasion of HCC cells. Conclusions: miR-718 acts as a tumor suppressive microRNA in HCC via regulating the expression of EGR3, which may provide a new diagnostic 07) found that overexpreget for HCC.
文摘Objective To explore the expression of etheràgo-go1(Eag1)in human osteosarcoma and its molecular mechanisms of regulating the malignant phenotype of osteosarcoma.Methods The expression levels of Eag1 in osteosarcoma cell lines and human osteosarcoma tissues were detected by reverse transcription polymerase chain reaction(RT-PCR),western blot analysis and immunohistochemistry.The small interfering RNA(siRNA)was
基金This work was supported by the Basic Research Program of Yunnan Province-Joint Project of Kunming Medical University No.202101AY070001−169.
文摘Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective treatment.In this investigation,we explored the functional interaction of miR-30a-5p and the putative transcription factor 2 of the homeodomain(PHTF2)in dictating the aggressiveness and metastasis of lung adenocarcinoma.Method:We collected clinical samples to evaluate the expression patterns of miR-30a-5p and PHTF2 in lung adenocarcinoma along with normal tissues.Cellular experiments including cell count kit(CCK)-8 growth assay,apoptosis analysis,migration and invasion examinations were performed to assess the aggressiveness of lung adenocarcinoma cells.Furthermore,we examined tumorigenesis and metastasis in a nude mouse model.Results:MiR-30a-5p exhibited downregulation pattern in lung adenocarcinoma samples.Transfection of miR-30a-5p mimic in lung adenocarcinoma cells resulted in the suppression of malignant characteristics.Notably,the administration of miR-30a-5p mimic also curbed tumorigenesis and metastasis of lung adenocarcinoma cells in animal model.Moreover,PHTF2 was found to be a molecular target of miR-30a-5p.Upregulating PHTF2 counteracted the tumor-suppressive effect of the miR-30a-5p mimic.Conclusion:miR-30a-5p functions as a tumor-suppressive molecule while PHTF2 acts as an oncogenic factor in the development and metastasis of lung adenocarcinoma.Therefore,targeting miR-30a-5p and PHTF2 could be developed into a promising therapeutic approach for inhibiting metastasis in lung adenocarcinoma.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal neoplasms of the gastrointestinal tract.Surgical resection and tyrosine kinase inhibitors are defined as the main treatments but cannot cure patients with advanced GIST,which eventually develops into recurrence and acquired drug resistance.Therefore,it is necessary to identify prognostic biomarkers and new therapeutic targets for GISTs.CC chemokine receptor type 8(CCR8)protein participates in regulation of immune responses.Recent studies on CCR8 in nonsmall cell lung cancer and colorectal cancer showed that it was highly expressed in tumor-infiltrating regulatory T cells and correlated with a poor prognosis.AIM To detect CCR8 expression in GIST tissues and analyze its relationships with clinicopathological features and prognosis in patients with GISTs.METHODS Tissue samples were used for the tissue microarrays construction.The microarrays were then subjected to immunohistochemical analyses to detect CCR8 expression.Next,Kaplan–Meier analysis was utilized to calculate the survival rate of patients with complete follow-up data,and the potential prognostic value of CCR8 was evaluated by Cox regression analysis.Finally,a Gene Ontology/Kyoto Encyclopedia of Genes and Genomes single-gene enrichment chart of CCR8 was constructed using the STRING database.RESULTS CCR8-positive signals were detected as brown or brown-yellow particles by immunohistochemistry located in the cytoplasm.Among 125 tissue samples,74 had CCR8 high expression and 51 had low or negative expression.Statistical analyses suggested CCR8 was significantly correlated with tumor size,mitotic index,AFIP-Miettinen risk classification and tumor location.Kaplan–Meier and multivariate analyses showed that patients with low or negative CCR8 expression,mitotic index<5/high-power fields(HPF)and tumor diameter<5 cm had a better prognosis.Based on the STRING database,CCR8 was significantly enriched in biological processes such as tumor immunity,T lymphocyte chemotaxis,migration and pathways like the nuclear factor-κB and tumor necrosis factor pathways as well as intestinal immune regulation networks.CONCLUSION CCR8 is a prognostic biomarker for malignant potential of GISTs,with high expression correlated with malignancy and poor prognosis.