Zinc finger protein 831 promotes apoptosis and enhances chemosensitivity in breast cancer by acting as a novel transcriptional repressor targeting the STAT3/Bcl2 signaling pathway  

作　　者：Jun Fan Zhe Zhang Hongqiang Chen Dongjiao Chen Wenbo Yuan Jingzhi Li Yong Zeng Shimeng Zhou Shu Zhang Gang Zhang Jiashen Xiong Lu Zhou Jing Xu Wenbin Liu Yan Xu 

机构地区：[1]Department of Breast and Thyroid Surgery,Daping Hospital,Army Medical University(Third Military Medical University),Chongqing 400042,China [2]Institute of Toxicology,College of Preventive Medicine,Army Medical University(Third Military Medical University),Chongqing 400038,China [3]Department of Environmental Health,College of Preventive Medicine,Army Medical University(Third Military Medical University),Chongqing 400038,China [4]Anesthesia and Intensive Care,Chinese University of Hong Kong,Hong Kong SAR 999077,China [5]School of Public Health,Xinxiang Medical University,Xinxiang,Henan 453003,China [6]School of Public Health,China Medical University,Shenyang,Liaoning 110122,China

出　　处：《Genes & Diseases》2024年第1期430-448,共19页基因与疾病（英文）

基　　金：supported by the National Natural Science Foundation of China(No.81472482,82173556);the Clinical Technology Innovation and Cultivation Project of the Army Medical University of China(No.CX2019LC120);the National Key Clinical Specialty Military Construction Project(China,No.425Z8).

摘　　要：Emerging evidence suggested that zinc finger protein 831(ZNF831)was associated with immune activity and stem cell regulation in breast cancer.Whereas,the roles and molec-ular mechanisms of ZNF831 in oncogenesis remain unclear.ZNF831 expression was significantly diminished in breast cancer which was associated with promoter CpG methylation but not mu-tation.Ectopic over-expression of ZNF831 suppressed breast cancer cell proliferation and col-ony formation and promoted apoptosis in vitro,while knockdown of ZNF831 resulted in an opposite phenotype.Anti-proliferation effect of ZNF831 was verified in vivo.Bioinformatic analysis of public databases and transcriptome sequencing both showed that ZNF831 could enhance apoptosis through transcriptional regulation of the JAK/STAT pathway.ChiP and luciferase report assays demonstrated that ZNF831 could directly bind to one specific region of STAT3 promoter and induce the transcriptional inhibition of STAT3.As a result,the attenuation of STAT3 led to a restraint of the transcription of Bcl2 and thus accelerated the apoptotic progression.Augmentation of STAT3 diminished the apoptosis-promoting effect of ZNF831 in breast cancer cell lines.Furthermore,ZNF831 could ameliorate the anti-proliferation effect of capecitabine and gemcitabine in breast cancer cell lines.Our findings demonstrate for the first time that ZNF831 is a novel transcriptional suppressor through inhibiting the expression of STAT3/Bcl2 and promoting the apoptosis process in breast cancer,suggesting ZNF831 as a novel biomarker and potential therapeutic target for breast cancer patients.

关 键 词：Apoptosis Breast cancer CHEMOSENSITIVITY STAT3 ZNF831 

分 类 号：R73[医药卫生—肿瘤]