Hao Liang, Wang Jia-Mei, Liu Bao-Qin, Yan Jing, Li Chao, Jiang Jing-Yi, Zhao Fu-Ying, Qiao Huai-Yu, Wang Hua-Qin
Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110122, China; Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China; Department of Chemistry, China Medical University, Shenyang 110122, China.
Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110122, China.
Biochim Biophys Acta Mol Cell Res. 2021 Jan;1868(1):118878. doi: 10.1016/j.bbamcr.2020.118878. Epub 2020 Oct 1.
Ovarian cancer is the deadliest gynaecologic malignancy, and the five-year survival rate of patients is less than 35% worldwide. Cancer stem cells (CSCs) are a population of cells with stem-like characteristics that are thought to cause chemoresistance and recurrence. TRIM29 is aberrantly expressed in various cancers and associated with cancer development and progression. Previous studies showed that the upregulation of TRIM29 expression in pancreatic cancer is related to stem-like characteristics. However, the role of TRIM29 in ovarian cancer is poorly understood. In this study, we found that TRIM29 expression was increased at the translational level in both the cisplatin-resistant ovarian cancer cells and clinical tissues. Increased TRIM29 expression was associated with a poor prognosis of patients with ovarian cancer. In addition, TRIM29 could enhance the CSC-like characteristics of the cisplatin-resistant ovarian cancer cells. Recruitment of YTHDF1 to m6A-modified TRIM29 was involved in promoting TRIM29 translation in the cisplatin-resistant ovarian cancer cells. Knockdown of YTHDF1 suppressed the CSC-like characteristics of the cisplatin-resistant ovarian cancer cells, which could be rescued by ectopic expression of TRIM29. This study suggests TRIM29 may act as an oncogene to promote the CSC-like features of cisplatin-resistant ovarian cancer in an m6A-YTHDF1-dependent manner. Due to the roles of TRIM29 and YTHDF1 in the promotion of CSC-like features, they may become potential therapeutic targets to combat the recurrence of ovarian cancer.
卵巢癌是最致命的妇科恶性肿瘤，全球患者的五年生存率不到35%。癌症干细胞（CSCs）是一群具有干细胞样特征的细胞，被认为会导致化疗耐药性和复发。TRIM29在多种癌症中异常表达，并与癌症的发生和发展相关。先前的研究表明，胰腺癌中TRIM29表达的上调与干细胞样特征有关。然而，TRIM29在卵巢癌中的作用尚不清楚。在本研究中，我们发现TRIM29在顺铂耐药的卵巢癌细胞和临床组织中的翻译水平均升高。TRIM29表达的增加与卵巢癌患者的不良预后相关。此外，TRIM29可以增强顺铂耐药卵巢癌细胞的CSC样特征。YTHDF1募集到m6A修饰的TRIM29参与促进顺铂耐药卵巢癌细胞中TRIM29的翻译。敲低YTHDF1可抑制顺铂耐药卵巢癌细胞的CSC样特征，而TRIM29的异位表达可挽救这种抑制作用。本研究表明，TRIM29可能作为一种癌基因，以m6A-YTHDF1依赖的方式促进顺铂耐药卵巢癌的CSC样特征。由于TRIM29和YTHDF1在促进CSC样特征方面的作用，它们可能成为对抗卵巢癌复发的潜在治疗靶点。
