miR-34b-3p-mediated regulation of STC2 and FN1 enhances chemosensitivity and inhibits proliferation in cervical cancer  

作　　者：Shanshan Jin Wenting Wang Xinrui Xu Zhaowei Yu Zihan Feng Jun Xie Huimin Lv 

机构地区：[1]Department of Biochemistry and Molecular Biology,Shanxi Key Laboratory of Birth Defect and Cell Regeneration,Key Laboratory for Cellular Physiology of Ministry of Education,Shanxi Medical University,Taiyuan 030001,China [2]Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital,Third Hospital of Shanxi Medical University,Taiyuan 030032,China [3]Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第5期740-752,共13页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the Applied Basic Research Programs of Science and Technology Commission Foundation of Shanxi Province(No.20210302124592);the Scientific Research Project of Health Commission of Shanxi Province(No.2021151).

摘　　要：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 regulates 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 STC2 and 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 demonstrate 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.

关 键 词：miR-34b-3p CHEMORESISTANCE cervical cancer stanniocalcin 2(STC2) fibronectin 1(FN1) CISPLATIN 

分 类 号：R730.53[医药卫生—肿瘤]