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RNA结合蛋白QKI5通过下调转录共激活因子TAZ抑制卵巢癌。

The RNA binding protein QKI5 suppresses ovarian cancer via downregulating transcriptional coactivator TAZ.

作者信息

Liu Tao, Yang Yu, Xie Zhe, Luo Qingya, Yang Dan, Liu Xiaoyi, Zhao Hongyan, Wei Qinglv, Liu Yi, Li Lanfang, Wang Yuya, Wang Fang, Yu Jianhua, Xu Jing, Yu Jia, Yi Ping

机构信息

Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China.

Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing 400042, China.

出版信息

Mol Ther Nucleic Acids. 2021 Jul 29;26:388-400. doi: 10.1016/j.omtn.2021.07.012. eCollection 2021 Dec 3.

Abstract

RNA-binding proteins (RBPs) are a set of proteins involved in many steps of post-transcriptional regulation to maintain cellular homeostasis. Ovarian cancer (OC) is the most deadly gynecological cancer, but the roles of RBPs in OC are not fully understood. Here, we reported that the RBP QKI5 was significantly negatively correlated with aggressive tumor stage and worse prognosis in serous OC patients. QKI5 could suppress the growth and metastasis of OC cells both and . Transcriptome analysis showed that QKI5 negatively regulated the expression of the transcriptional coactivator TAZ and its downstream targets (e.g., CTGF and CYR61). Mechanistically, QKI5 bound to TAZ mRNA and recruited EDC4, thus decreasing the stability of TAZ mRNA. Functionally, TAZ was involved in the QKI5-mediated tumor suppression of OC cells, and QKI5 expression was inversely correlated with TAZ, CTGF, and CYR61 expression in OC patients. Together, our study indicates that QKI5 plays a tumor-suppressive role and negatively regulates TAZ expression in OC.

摘要

RNA结合蛋白(RBPs)是一组参与转录后调控多个步骤以维持细胞稳态的蛋白质。卵巢癌(OC)是最致命的妇科癌症,但RBPs在OC中的作用尚未完全明确。在此,我们报告RBP QKI5与浆液性OC患者的侵袭性肿瘤分期和较差预后显著负相关。QKI5在体内和体外均可抑制OC细胞的生长和转移。转录组分析表明,QKI5负向调节转录共激活因子TAZ及其下游靶点(如CTGF和CYR61)的表达。机制上,QKI5与TAZ mRNA结合并募集EDC4,从而降低TAZ mRNA的稳定性。功能上,TAZ参与了QKI5介导的OC细胞肿瘤抑制作用,且OC患者中QKI5表达与TAZ、CTGF和CYR61表达呈负相关。总之,我们的研究表明QKI5在OC中发挥肿瘤抑制作用并负向调节TAZ表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/177f/8426461/b41bd8115627/fx1.jpg

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