Silencing miRNA-155 inhibits the proliferation,invasion and migration of endometrial cancer cells
Objective To investigate the effect of microRNA-155(miR-155)on the occurrence and development of endometrial carcinoma and the regulation of hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)pathway.Methods Human normal endometrial epithelial cells(hEEC)and human endometrial cancer cell lines(HEC-1A,HHUA)were collected,and the expression levels of miR-155,HIF-1α and VEGF genes were detected by RT-qPCR.HEC-1A cells were divided into control group,miR-155-inhibitor group,miR-155 negative control(miR-155-iNC)group,and HIF-1α/VEGF signal pathway blocker(YC-1)group.RT-qPCR was used to detect the expression level of miR-155 in each group,Western blot was used to detect the expression level of HIF-1α and VEGF protein;CCK-8 methods was used to detect cell proliferation activity;the tumorigenic ability was detected in nude mice;cell migration and invasion ability were detected by Transwell cell assay;the relative expression levels of cell proliferation marker protein(Ki67)and extracellular matrix met-alloproteinase(MMP-7)were detected by Western blot.The HEC-1 A cells were further divided into miR-155-inhibitor+HIF-1α agonist(DMOG)group,miR-155-NC+DMOG group,DMOG group,miR-155-NC group,miR-155-inhibitor group,untransfected group(control group),the expression levels of proteins related to cell proliferation,invasion and migration in each group were detected.Results Compared with hEEC cells,the expressions of miR-155,HIF-1α and VEGF genes in HEC-1A and HHUA were all increased(P＜0.05),and the above genes expressed the highest in HEC-1A cell lines.After down-regulating miR-155 or blocking the HIF-1α/VEGF signaling pathway,cell proliferation,invasion and migration,tu-morigenesis and the expression of HIF-1α,VEGF,Ki67,and MMP-7 proteins were all reduced(P＜0.05).After the down-regulation of miR-155 and HIF-1α activator co-acted,while the cellular HIF-1α/VEGF pathway was activated,the ex-pression of cell proliferation and migration-related proteins was also higher than that in the miR-155 group alone(P＜0.05).Conclusion The expression of miR-155 and HIF-1α/VEGF pathway in endometrial carcinoma cells is increased.Down regu-lation of miR-155 expression can inhibit the activation of HIF-1α/VEGF pathway and inhibit the proliferation,invasion and migration of endometrial cancer cells.
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