BACKGROUND Recent studies have proved the important role of many oncogenic long noncoding RNAs(lncRNAs) in the progression of pancreatic cancer, but little is known about the mechanisms of tumor suppression in pancrea...BACKGROUND Recent studies have proved the important role of many oncogenic long noncoding RNAs(lncRNAs) in the progression of pancreatic cancer, but little is known about the mechanisms of tumor suppression in pancreatic cancer.AIM To evaluate the function of tumor suppressor lncRNA C9orf139 in pancreatic cancer progression and to study the underlying mechanism.METHODS We assigned 54 patients with pancreatic ductal adenocarcinoma treated at our hospital to the patient group and 30 normal subjects undergoing physical examination to the control group. RT-qPCR was used to measure the relative expression of C9orf139 in the tissue and serum of patients, in an attempt to investigate the prognostic value of C9orf139 in pancreatic cancer patients. The luciferase reporter gene assay was performed to determine the interaction between C9orf139 and miR-663 a. The biological function of C9orf139 was assessed by in vitro assays and in vivo subcutaneous tumor formation tests in animal models. To figure out the molecular mechanism of C9orf139 to act on miR-663 a/Sox12, RNA pull-down, Western blot assay, RNA immunoprecipitation assay, and co-immunoprecipitation assay were performed.RESULTS C9orf139 level significantly increased in the tissue and serum of patients, which had clinical diagnostic value for pancreatic cancer. Patients with high C9orf139 expression had a higher risk of progressing to stage Ⅲ + Ⅳ, lymph node metastasis, and poor differentiation. Cox regression analysis suggested that C9orf139, tumor-node-metastasis stage, and lymph node metastasis were independent prognostic factors in patients. The underlying mechanism of C9orf139 was that it promoted the growth of pancreatic cancer cells by modulating the miR-663 a/Sox12 axis.CONCLUSION C9orf139 is highly expressed in pancreatic cancer, qualified to be used as a potential diagnostic and prognostic marker for pancreatic cancer. Its promotion of pancreatic cancer cell growth is achieved by mediating the miR-663 a/Sox12 axis.展开更多
Allergic asthma that is caused by inhalation of house dust mites(HDMs)is mainly mediated by Th2 cells.Recently,the roles of Sox(SRY-related high-mobility-group(HMG)-box)family members in various immune responses have ...Allergic asthma that is caused by inhalation of house dust mites(HDMs)is mainly mediated by Th2 cells.Recently,the roles of Sox(SRY-related high-mobility-group(HMG)-box)family members in various immune responses have been investigated.However,the roles of Sox12,a member of the SoxC group,in Th2 cell differentiation and allergic airway inflammation,remain unknown.We showed that Sox12 mRNA was significantly increased during Th2 cell differentiation.In vivo,HDM-induced eosinophil infiltration into the lung and Th2 cell differentiation were exacerbated in Sox12−/−mice compared with those in control Sox12+/−mice.In vitro,Sox12−/−CD4^(+)T cells that were cultured under Th2 conditions had increased production of Th2 cytokines and GATA3 protein compared with those of control Sox12+/−CD4^(+)T cells.Importantly,forced expression of Sox12 decreased the protein levels of GATA3 in CD4^(+)T cells under Th2 conditions without affecting mRNA expression.Furthermore,Sox12 induced degradation of GATA3 through the proteasome pathway in CD4^(+)T cells.Consistently,Sox12 enhanced ubiquitination of GATA3,which was mediated by the E3 ligase Fbw7.Finally,we found that Fbw7 knockdown partly abrogated Sox12-mediated GATA3 suppression in CD4^(+)T cells.Taken together,these results suggest that Sox12 suppresses Th2 cell differentiation by accelerating Fbw7-mediated GATA3 degradation,and attenuates HDM-induced allergic inflammation.展开更多
文摘BACKGROUND Recent studies have proved the important role of many oncogenic long noncoding RNAs(lncRNAs) in the progression of pancreatic cancer, but little is known about the mechanisms of tumor suppression in pancreatic cancer.AIM To evaluate the function of tumor suppressor lncRNA C9orf139 in pancreatic cancer progression and to study the underlying mechanism.METHODS We assigned 54 patients with pancreatic ductal adenocarcinoma treated at our hospital to the patient group and 30 normal subjects undergoing physical examination to the control group. RT-qPCR was used to measure the relative expression of C9orf139 in the tissue and serum of patients, in an attempt to investigate the prognostic value of C9orf139 in pancreatic cancer patients. The luciferase reporter gene assay was performed to determine the interaction between C9orf139 and miR-663 a. The biological function of C9orf139 was assessed by in vitro assays and in vivo subcutaneous tumor formation tests in animal models. To figure out the molecular mechanism of C9orf139 to act on miR-663 a/Sox12, RNA pull-down, Western blot assay, RNA immunoprecipitation assay, and co-immunoprecipitation assay were performed.RESULTS C9orf139 level significantly increased in the tissue and serum of patients, which had clinical diagnostic value for pancreatic cancer. Patients with high C9orf139 expression had a higher risk of progressing to stage Ⅲ + Ⅳ, lymph node metastasis, and poor differentiation. Cox regression analysis suggested that C9orf139, tumor-node-metastasis stage, and lymph node metastasis were independent prognostic factors in patients. The underlying mechanism of C9orf139 was that it promoted the growth of pancreatic cancer cells by modulating the miR-663 a/Sox12 axis.CONCLUSION C9orf139 is highly expressed in pancreatic cancer, qualified to be used as a potential diagnostic and prognostic marker for pancreatic cancer. Its promotion of pancreatic cancer cell growth is achieved by mediating the miR-663 a/Sox12 axis.
基金supported in part by Grants-in-Aids for Scientific Research from the Ministry of Education,Culture,Sports,Science,and Technology,the Japanese Government,the LGS(Leading Graduate School at Chiba University)Program,MEXT,and the Institute for Global Prominent Research,Chiba University,Japan.
文摘Allergic asthma that is caused by inhalation of house dust mites(HDMs)is mainly mediated by Th2 cells.Recently,the roles of Sox(SRY-related high-mobility-group(HMG)-box)family members in various immune responses have been investigated.However,the roles of Sox12,a member of the SoxC group,in Th2 cell differentiation and allergic airway inflammation,remain unknown.We showed that Sox12 mRNA was significantly increased during Th2 cell differentiation.In vivo,HDM-induced eosinophil infiltration into the lung and Th2 cell differentiation were exacerbated in Sox12−/−mice compared with those in control Sox12+/−mice.In vitro,Sox12−/−CD4^(+)T cells that were cultured under Th2 conditions had increased production of Th2 cytokines and GATA3 protein compared with those of control Sox12+/−CD4^(+)T cells.Importantly,forced expression of Sox12 decreased the protein levels of GATA3 in CD4^(+)T cells under Th2 conditions without affecting mRNA expression.Furthermore,Sox12 induced degradation of GATA3 through the proteasome pathway in CD4^(+)T cells.Consistently,Sox12 enhanced ubiquitination of GATA3,which was mediated by the E3 ligase Fbw7.Finally,we found that Fbw7 knockdown partly abrogated Sox12-mediated GATA3 suppression in CD4^(+)T cells.Taken together,these results suggest that Sox12 suppresses Th2 cell differentiation by accelerating Fbw7-mediated GATA3 degradation,and attenuates HDM-induced allergic inflammation.
