RNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression

• DOI: 10.1111/cas.14280
• Publication Date: 2019-12-13T13:16:27Z
• Authors: Jing Zhao; Yu Zhang; Xi‐sheng Liu; Fang‐ming Zhu; Feng Xie; Chen‐yi Jiang; Zi‐ye Zhang; Ying‐li Gao; Yong‐chuan Wang; Bin Li; Shu‐jie Xia; Bang‐min Han
• Keywords: Male; 0301 basic medicine; RNA Stability; Prostatic Neoplasms; RNA-Binding Proteins; Original Articles; Up-Regulation; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; Receptors, Androgen; Cell Line, Tumor; Disease Progression; Animals; Humans; Neoplasm Grading; 3' Untranslated Regions; Neoplasm Transplantation

Abstract The androgen receptor (AR) pathway is critical for prostate cancer carcinogenesis and development; however, after 18‐24 months of AR blocking therapy, patients invariably progress to castration‐resistant (CRPC), which remains an urgent problem be solved. Therefore, finding key molecules that interact with as novel strategies treat even CRPC desperately needed. In the current study, we focused on regulation RNA‐binding proteins (RBPs) associated determined mRNA protein levels were highly correlated Musashi2 (MSI2) levels. MSI2 was upregulated in specimens significantly advanced tumor grades. Downregulation both sensitive insensitive cells inhibited formation vivo decreased cell growth vitro, could reversed by overexpression. Mechanistically, directly bound 3′‐untranslated region (UTR) increase its stability and, thus, enhanced transcriptional activity. Our findings illustrate a previously unknown regulatory mechanism proliferation regulated MSI2‐AR axis provide evidence towards strategy against cancer.