Wang Xu, Wei Xiaolin, Cao Yu, Xing Peng
Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Am J Pathol. 2022 Oct;192(10):1458-1469. doi: 10.1016/j.ajpath.2022.06.010. Epub 2022 Jul 16.
Overexpression of ZNF33A (Krüppel-type zinc finger 33A) promotes carcinogenesis in several malignant tumors. However, the biochemical role and clinical importance of ZNF33A in triple-negative breast cancer (TNBC) still need to be explored. In this study, overexpression of ZNF33A in TNBC patient tissues and cell lines led to a worse prognosis. ZNF33A promoted cell growth and facilitated the resistance of cancer cells to inhibitors of bromodomain and extraterminal domain (BET) in TNBC. ZNF33A also promoted the induction of c-Myc, the primary player for the resistance to BET inhibitors in TNBC. In conclusion, ZNF33A may be a tumor growth-promoting factor associated with TNBC prognosis, and ZNF33A repression may sensitize TNBC cells to BET inhibitors.
锌指蛋白33A（ZNF33A，克鲁ppel型锌指蛋白33A）的过表达促进了多种恶性肿瘤的致癌作用。然而，ZNF33A在三阴性乳腺癌（TNBC）中的生化作用和临床重要性仍有待探索。在本研究中，TNBC患者组织和细胞系中ZNF33A的过表达导致预后较差。ZNF33A促进细胞生长，并促进TNBC癌细胞对溴结构域和额外末端结构域（BET）抑制剂的抗性。ZNF33A还促进了c-Myc的诱导，c-Myc是TNBC中对BET抑制剂抗性的主要因素。总之，ZNF33A可能是与TNBC预后相关的肿瘤生长促进因子，抑制ZNF33A可能使TNBC细胞对BET抑制剂敏感。
