BACKGROUND Studies have reported that microRNA-30c(miR-30c)has vital functions in the development and progression of multiple cancers.AIM To investigate the clinical significance and role of miR-30c in pancreatic canc...BACKGROUND Studies have reported that microRNA-30c(miR-30c)has vital functions in the development and progression of multiple cancers.AIM To investigate the clinical significance and role of miR-30c in pancreatic cancer.METHODS MiR-30c and twinfilin 1(TWF1)expression levels were analyzed in Gene Expression Omnibus datasets and validated in human pancreatic cancer by quantitative real-time polymerase chain reaction(RT-qPCR).The effects of miR-30c on pancreatic cancer cell growth,apoptosis,and cell cycle were evaluated by CCK-8 and flow cytometry assays.Furthermore,the in vivo effects were investigated using a subcutaneous xenograft experiment.Target gene prediction software and luciferase reporter assays were used to identify TWF1 as a direct target of miR-30c.RESULTS The expression of miR-30c was significantly decreased in pancreatic cancer tissues and associated with survival.Gain-and loss-of-function assays showed that miR-30c suppressed pancreatic cancer cell proliferation in vitro and in vivo.RT-qPCR,Western blot,and luciferase reporter assays showed that miR-30c directly targeted TWF1.The expression level of miR-30c was negatively correlated with TWF1 expression in pancreatic cancer tissues.Furthermore,the effects of ectopic miR-30c were rescued by TWF1 overexpression.CONCLUSION Our results identified the role of the miR-30c/TWF1 axis in pancreatic cancer progression and demonstrated that miR-30c might serve as a prognostic biomarker and therapeutic target for pancreatic cancer.展开更多
Objective Gastrointestinal stromal tumors(GISTs)can rapidly proliferate through angiogenesis.Previous studies indicated the potential influence of microRNA on the progression of tumor immature angiogenesis.This study ...Objective Gastrointestinal stromal tumors(GISTs)can rapidly proliferate through angiogenesis.Previous studies indicated the potential influence of microRNA on the progression of tumor immature angiogenesis.This study aimed to explore the specific mechanism by which microRNA-409-5p(miR-409-5p)contributes to GIST.Methods To identify genes potentially involved in the development and progression of GIST,the differences of miR-409-5p between tumors and adjacent tissues were first analyzed.Following this analysis,target genes were predicted.To further investigate the function of miRNA in GIST cells,two GIST cell lines(GIST-T1 and GIST882)were transfected with lentiviruses that stably expressed miR-409-5p and scrambled miRNA(negative control).Later,the cells were subjected to Western blotting and ELSA to determine any differences in angiogenesis-related genes.Results In GISTs,there was a decrease in the expression levels of miR-409-5p compared to the adjacent tissues.It was observed that the upregulation of miR-409-5p in GIST cell lines effectively inhibited the proteins hypoxia-inducible transcription factor 1β(HIF1β)and vascular endothelial growth factor A(VEGF-A).Further investigations revealed that miR-409-5p acted as an inhibitor of angiogenesis by binding to the 3′-UTR of Lysine-specific demethylase 4D(KDM4D)mRNA.Moreover,the combination of miR-409-5p with imatinib enhanced its inhibitory effect on angiogenesis.Conclusion This study demonstrated that the miRNA-409-5p/KDM4D/HIF1β/VEGF-A signaling pathway could serve as a novel target for the development of therapeutic strategies for the treatment of imatinib-resistance in GIST patients.展开更多
基金Supported by the National Nature Science Foundation of China,No.61802350
文摘BACKGROUND Studies have reported that microRNA-30c(miR-30c)has vital functions in the development and progression of multiple cancers.AIM To investigate the clinical significance and role of miR-30c in pancreatic cancer.METHODS MiR-30c and twinfilin 1(TWF1)expression levels were analyzed in Gene Expression Omnibus datasets and validated in human pancreatic cancer by quantitative real-time polymerase chain reaction(RT-qPCR).The effects of miR-30c on pancreatic cancer cell growth,apoptosis,and cell cycle were evaluated by CCK-8 and flow cytometry assays.Furthermore,the in vivo effects were investigated using a subcutaneous xenograft experiment.Target gene prediction software and luciferase reporter assays were used to identify TWF1 as a direct target of miR-30c.RESULTS The expression of miR-30c was significantly decreased in pancreatic cancer tissues and associated with survival.Gain-and loss-of-function assays showed that miR-30c suppressed pancreatic cancer cell proliferation in vitro and in vivo.RT-qPCR,Western blot,and luciferase reporter assays showed that miR-30c directly targeted TWF1.The expression level of miR-30c was negatively correlated with TWF1 expression in pancreatic cancer tissues.Furthermore,the effects of ectopic miR-30c were rescued by TWF1 overexpression.CONCLUSION Our results identified the role of the miR-30c/TWF1 axis in pancreatic cancer progression and demonstrated that miR-30c might serve as a prognostic biomarker and therapeutic target for pancreatic cancer.
基金supported by the National Natural Science Foundation of China(No.81372323 and No.81802426).
文摘Objective Gastrointestinal stromal tumors(GISTs)can rapidly proliferate through angiogenesis.Previous studies indicated the potential influence of microRNA on the progression of tumor immature angiogenesis.This study aimed to explore the specific mechanism by which microRNA-409-5p(miR-409-5p)contributes to GIST.Methods To identify genes potentially involved in the development and progression of GIST,the differences of miR-409-5p between tumors and adjacent tissues were first analyzed.Following this analysis,target genes were predicted.To further investigate the function of miRNA in GIST cells,two GIST cell lines(GIST-T1 and GIST882)were transfected with lentiviruses that stably expressed miR-409-5p and scrambled miRNA(negative control).Later,the cells were subjected to Western blotting and ELSA to determine any differences in angiogenesis-related genes.Results In GISTs,there was a decrease in the expression levels of miR-409-5p compared to the adjacent tissues.It was observed that the upregulation of miR-409-5p in GIST cell lines effectively inhibited the proteins hypoxia-inducible transcription factor 1β(HIF1β)and vascular endothelial growth factor A(VEGF-A).Further investigations revealed that miR-409-5p acted as an inhibitor of angiogenesis by binding to the 3′-UTR of Lysine-specific demethylase 4D(KDM4D)mRNA.Moreover,the combination of miR-409-5p with imatinib enhanced its inhibitory effect on angiogenesis.Conclusion This study demonstrated that the miRNA-409-5p/KDM4D/HIF1β/VEGF-A signaling pathway could serve as a novel target for the development of therapeutic strategies for the treatment of imatinib-resistance in GIST patients.
