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Long noncoding RNA GAS5 interacts and suppresses androgen receptor activity in prostate cancer cells
Author(s) -
Lv Shidong,
Pu Xiaochun,
Luo Mayao,
Wen Haoran,
Xu Zhuofan,
Wei Qiang,
Dang Qiang
Publication year - 2021
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.24186
Subject(s) - transactivation , gas5 , androgen receptor , gene knockdown , prostate cancer , cancer research , long non coding rna , downregulation and upregulation , androgen deprivation therapy , small hairpin rna , biology , transcription factor , apoptosis , medicine , cancer , gene , biochemistry
Abstract The androgen receptor (AR) plays an important role in the progression of prostate cancer and is the most important therapeutic target. However, androgen deprivation therapy will finally lead patients to progress to castration‐resistant prostate cancer (CRPC). Here, we confirmed that GAS5, a long noncoding RNA, could interact and suppress AR transactivation in CRPC C4‐2 cells. Knockdown GAS5 by short hairpin RNA would enhance the transcription of AR via promote AR recruitment to the promoter of its downstream target genes. Functionally, GAS5 overexpression inhibits cell proliferation partially through inhibiting AR transactivation in C4‐2 cells. Moreover, knocking down GAS5 protects C4‐2 cells from the docetaxel‐induced cell apoptosis. In return, the suppressed AR was found to downregulate the GAS5 expression, which forms a feedback loop resulted in AR high transcription activity in CRPC. Collectively, our findings revealed the important role of GAS5 in AR axis activity regulation and CRPC progression. Targeting GAS5 to intervene the feedback loop might be a new potential therapeutic approach for the patients at CRPC stage.