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
- Genes & Diseases Vol. 1, Issue 1, Pages: 430-448(2024)
- 作者机构：
1. Department of Breast and Thyroid Surgery, Daping Hospital, Army Medical University (Third Military Medical University),Chongqing,China,400042
2. Institute of Toxicology, College of Preventive Medicine, Army Medical University (Third Military Medical University),Chongqing,China,400038
3. Department of Environmental Health, College of Preventive Medicine, Army Medical University (Third Military Medical University),Chongqing,China,400038
4. Anesthesia and Intensive Care, Chinese University of Hong Kong,Hong Kong SAR,China,999077
5. School of Public Health, Xinxiang Medical University,Henan,Xinxiang,China,453003
6. School of Public Health, China Medical University,Liaoning,Shenyang,China,110122
- 作者简介：
- 基金信息：
DOI：10.1016/j.gendis.2022.11.023
CLC：Published：2024，
Published Online：1 January 2024，
扫 描 看 全 文
Jun Fan, Zhe Zhang, Hongqiang Chen, et al. 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. [J]. Genes & Diseases 1(1):430-448(2024)
Jun Fan, Zhe Zhang, Hongqiang Chen, et al. 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. [J]. Genes & Diseases 1(1):430-448(2024) DOI： 10.1016/j.gendis.2022.11.023.
摘要
Abstract
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 molecular mechanisms of
ZNF831
in oncogenesis remain unclear.
ZNF831
expression was significantly diminished in breast cancer which was associated with promoter CpG methylation but not mutation. Ectopic over-expression of
ZNF831
suppressed breast cancer cell proliferation and colony 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
/
Bcl
2 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
Keywords
ApoptosisBreast cancerChemosensitivitySTAT3ZNF831
references
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