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

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.