DNA methyltransferase 1/miR-342-3p/Forkhead box M1 signaling axis promotes self-renewal in cervical cancer stem-like cells in vitro and nude mice models  

作　　者：Xiao-Zheng Cao Yao-Feng Zhang Yu-Wei Song Lei Yuan Hui-Li Tang Jin-Yuan Li Ye-Bei Qiu Jia-Zhi Lin Ying-Xia Ning Xiao-Yu Wang Yong Xu Shao-Qiang Lin 

机构地区：[1]Guangdong Provincial Engineering Research Center for Esophageal Cancer Precise Therapy,The First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 510062,Guangdong Province,China [2]Institute of Drug Discovery,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,Guangdong Province,China [3]School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 510006,Guangdong Province,China [4]Central Laboratory,The First Affiliated Hospital of Jinan University,Guangzhou 510630,Guangdong Province,China [5]Central Laboratory,The Affiliated Shunde Hospital of Jinan University,Foshan 528000,Guangdong Province,China [6]Department of Pelvic Radiotherapy,Meizhou People’s Hospital,Meizhou 514030,Guangdong Province,China [7]Department of Oncology,The First Affiliated Hospital of Jinan University,Guangzhou 510630,Guangdong Province,China [8]Department of Gynaecology and Obstetrics,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou 510000,Guangdong Province,China

出　　处：《World Journal of Stem Cells》2025年第3期44-64,共21页世界干细胞杂志(英文)

基　　金：Supported by Guangzhou Basic and Applied Basic Research Foundation,No.202201010121;Medical Joint Fund of Jinan University,No.YXZY2024014 and No.YXJC2022001;Hospital Achievement Transformation and Cultivation Project,No.ZH201911;the Key Discipline Project of Guangdong Province,No.2019-GDXK-0016;and the Medical Science and Technology Research Foundation of Guangdong Province,No.B2021145.

摘　　要：BACKGROUND Cervical cancer(CC)stem cell-like cells(CCSLCs),defined by the capacity of differentiation and self-renewal and proliferation,play a significant role in the progression of CC.However,the molecular mechanisms regulating their self-renewal are poorly understood.Therefore,elucidation of the epigenetic mechanisms that drive cancer stem cell self-renewal will enhance our ability to improve the effectiveness of targeted therapies for cancer stem cells.AIM To explore how DNA methyltransferase 1(DNMT1)/miR-342-3p/Forkhead box M1(FoxM1),which have been shown to have abnormal expression in CCSLCs,and their signaling pathways could stimulate self-renewal-related stemness in CCSLCs.METHODS Sphere-forming cells derived from CC cell lines HeLa,SiHa and CaSki served as CCSLCs.Self-renewal-related stemness was identified by determining sphere and colony formation efficiency,CD133 and CD49f protein level,and SRY-box transcription factor 2 and octamer-binding transcription factor 4 mRNA level.The microRNA expression profiles between HeLa cells and HeLa-derived CCSLCs or mRNA expression profiles that HeLaderived CCSLCs were transfected with or without miR-342-3p mimic were compared using quantitative PCR analysis.The expression levels of DNMT1 mRNA,miR-342-3p,and FoxM1 protein were examined by quantitative real-time PCR and western blotting.In vivo carcinogenicity was assessed using a mouse xenograft model.The functional effects of the DNMT1/miR-342-3p/FoxM1 axis were examined by in vivo and in vitro gain-of-activity and loss-of-activity assessments.Interplay among DNMT1,miR-342-3p,and FoxM1 was tested by methylationspecific PCR and a respective luciferase reporter assay.RESULTS CCSLCs derived from the established HeLa cell lines displayed higher self-renewal-related stemness,including enhanced sphere and colony formation efficiency,increased CD133 and CD49f protein level,and heightened transcriptional quantity of stemness-related factors SRY-box transcription factor 2 and octamer-binding transcription factor 4 in vitro

关 键 词：DNA methyltransferase 1 Cancer stem cell Cervical cancer MiR-342-3p Forkhead box M1 

分 类 号：R73[医药卫生—肿瘤]