Zinc-finger protein 382 antagonises CDC25A and ZEB1 signaling pathway in breast cancer

Shuman Li; Xiaoqian He; Yan Wang; Weihong Chen; Ran Sun; Shaorong Tian; Sanxiu He; Chunyun Pu; Chen Li; Dishu Zhou; Yu Jiang; Qian Tao; Lili Li; Lin Ye; Yue Wu; Weiyan Peng; Tingxiu Xiang

doi:10.1016/j.gendis.2021.12.019

Zinc-finger protein 382 antagonises CDC25A and ZEB1 signaling pathway in breast cancer

Genes Dis. 2022 Feb 9;10(2):568-582. doi: 10.1016/j.gendis.2021.12.019. eCollection 2023 Mar.

Authors

Shuman Li^{1

2}, Xiaoqian He³, Yan Wang³, Weihong Chen³, Ran Sun³, Shaorong Tian³, Sanxiu He³, Chunyun Pu³, Chen Li⁴, Dishu Zhou³, Yu Jiang³, Qian Tao⁴, Lili Li⁴, Lin Ye³, Yue Wu³, Weiyan Peng³, Tingxiu Xiang^{2

3}

Affiliations

¹ Department of Oncology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
² Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China.
³ Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
⁴ Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir YK Pao Center for Cancer, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong and CUHK Shenzhen Research Institute, Shenzhen, Guangdong 518172, China.

Abstract

Our previous studies found that Zinc-finger protein 382 (ZNF382) played as a tumor suppressor gene in esophageal and gastric cancers, and a positive correlation between the high expression of ZNF382 and better outcome in breast cancer patients. However, the biological roles and mechanisms of ZNF382 in breast cancer remains unclear. We detected ZNF382 expression by reverse-transcription PCR (RT-PCR) and real-time quantitative PCR (qRT-PCR) in breast cancer cells and tissues, and explored the impacts and mechanisms of ectopic ZNF382 expression in breast cancer cells in vitro and in vivo, respectively. Our results revealed that ZNF382 was significantly down-regulated in breast cancer tissues compared with adjacent non-cancer tissues. Restoration of ZNF382 expression in silenced breast cancer cells not only inhibited tumor cell colony formation, viability, migration and invasion, and epithelial-mesenchymal-transition (EMT), but also induced apoptosis and G0/G1 arrest. In conclusion, ZNF382 could induce G0/G1 cell cycle arrest through inhibiting CDC25A signaling, and, inhibit cell migration, invasion and EMT by antagonizing ZEB1 signaling in breast cancer cells.

Keywords: Breast cancer; CDC25A; EMT; ZEB1; ZNF382.