Abstract
Dysregulation of microRNA(miRNA)expression in cancer is a significant factor contributing to the progression of chemoresistance.The objective of this study is to explore the underlying mechanisms by which miR-34b-3p reg-ulates chemoresistance in cervical cancer(CC).Previous findings have demonstrated low expression levels of miR-34b-3p in both CC chemoresistant cells and tissues.In this study,we initially characterize the behavior of SiHa/DDP cells which are CC cells resistant to the chemotherapeutic drug cisplatin(DDP).Subsequently,miR-34b-3p mimics are transfected into SiHa/DDP cells.It is observed that overexpression of miR-34b-3p substantially inhibits the proliferation,migration,and invasion abilities of SiHa/DDP cells and also enhances their sensitivity to DDP-induced cell death.Quantitative RT-PCR and western blot analysis further reveal elevated expression levels of STC2and FN1 in SiHa/DDP cells,contrary to the expression pattern of miR-34b-3p.Moreover,STC2 and FN1 contribute to DDP resistance,proliferation,migration,invasion,and decreased apoptosis in CC cells.Through dual-luciferase assay analysis,we confirm that STC2 and FN1 are direct targets of miR-34b-3p in CC.Finally,rescue experiments de-monstrate that overexpression of either STC2 or FN1 can partially reverse the inhibitory effects of miR-34b-3p overexpression on chemoresistance,proliferation,migration and invasion in CC cells.In conclusion,our findings support the role of miR-34b-3p as a tumor suppressor in CC.This study indicates that targeting the miR-34b-3p/STC2 or FN1 axis has potential therapeutic implications for overcoming chemoresistance in CC patients.
基金项目
Applied Basic Research Programs of Science and Technology Commission Foundation of Shanxi Province(20210302124592)
Scientific Research Project of Health Commission of Shanxi Province(2021151)
国家科技期刊平台
NSTL
万方数据