Li Shuman, He Xiaoqian, Wang Yan, Chen Weihong, Sun Ran, Tian Shaorong, He Sanxiu, Pu Chunyun, Li Chen, Zhou Dishu, Jiang Yu, Tao Qian, Li Lili, Ye Lin, Wu Yue, Peng Weiyan, Xiang Tingxiu
Department of Oncology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China.
Genes Dis. 2022 Feb 9;10(2):568-582. doi: 10.1016/j.gendis.2021.12.019. eCollection 2023 Mar.
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 and , 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.
我们之前的研究发现，锌指蛋白382（ZNF382）在食管癌和胃癌中作为一种肿瘤抑制基因发挥作用，并且ZNF382的高表达与乳腺癌患者更好的预后呈正相关。然而，ZNF382在乳腺癌中的生物学作用和机制仍不清楚。我们通过逆转录PCR（RT-PCR）和实时定量PCR（qRT-PCR）检测了乳腺癌细胞和组织中ZNF382的表达，并分别探讨了异位表达ZNF382对乳腺癌细胞的影响及其机制。我们的结果显示，与相邻的非癌组织相比，ZNF382在乳腺癌组织中显著下调。在沉默的乳腺癌细胞中恢复ZNF382的表达不仅抑制了肿瘤细胞集落形成、活力、迁移和侵袭以及上皮-间质转化（EMT），还诱导了细胞凋亡和G0/G1期阻滞。总之，ZNF382可通过抑制CDC25A信号通路诱导G0/G1期细胞周期阻滞，并通过拮抗乳腺癌细胞中的ZEB1信号通路抑制细胞迁移、侵袭和EMT。
