Open AccessRNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression
Author(s) -
Zhao Jing,
Zhang Yu,
Liu Xisheng,
Zhu Fangming,
Xie Feng,
Jiang Chenyi,
Zhang Ziye,
Gao Yingli,
Wang Yongchuan,
Li Bin,
Xia Shujie,
Han Bangmin
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14280
Subject(s) - prostate cancer , androgen receptor , downregulation and upregulation , cancer research , carcinogenesis , cancer , untranslated region , prostate , messenger rna , androgen , rna binding protein , biology , medicine , endocrinology , gene , biochemistry , hormone
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 prostate cancer (CRPC), which remains an urgent problem to be solved. Therefore, finding key molecules that interact with AR as novel strategies to treat prostate cancer and even CRPC is desperately needed. In the current study, we focused on the regulation of RNA‐binding proteins (RBPs) associated with AR and determined that the mRNA and protein levels of AR were highly correlated with Musashi2 (MSI2) levels. MSI2 was upregulated in prostate cancer specimens and significantly correlated with advanced tumor grades. Downregulation of MSI2 in both androgen sensitive and insensitive prostate cancer cells inhibited tumor formation in vivo and decreased cell growth in vitro, which could be reversed by AR overexpression. Mechanistically, MSI2 directly bound to the 3′‐untranslated region (UTR) of AR mRNA to increase its stability and, thus, enhanced its transcriptional activity. Our findings illustrate a previously unknown regulatory mechanism in prostate cancer cell proliferation regulated by the MSI2‐AR axis and provide novel evidence towards a strategy against prostate cancer.