EXPERIMENTAL RESEARCH
PRMT5, regulated by lncRNA ZFAS1/miR-150-5p, promoted androgen-independent prostate cancer migration and invasion
,
 
,
 
,
 
,
 
 
 
More details
Hide details
1
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
2
Department of Pathology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei, China
Submission date: 2019-09-19
Final revision date: 2020-03-13
Acceptance date: 2020-04-05
Online publication date: 2020-08-06
 
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Prostate cancer (PCa) is the most common male genitourinary malignancy in the world. The protein arginine methyltransferase 5 (PRMT5) is one of the main members of the type II PRMT family, which was reported to regulate androgen-dependent PCa cell proliferation. However, the upstream regulators of PRMT5 and its effects on androgen-independent PCa metastasis remained unclear. In the present study, we investigated whether PRMT5 could be a novel diagnostic marker and be used as a therapeutic target in PCa, to explore the possible molecular mechanism, and to understand the clinical importance of PRMT5 in PCa.

Material and methods:
The present study evaluated PRMT5 expression levels in PCa and normal prostate samples using public datasets, including TCGA, GEPIA and GSE21032. Furthermore, CCK-8 assay, flow cytometer assay, and transwell assay were conducted to detect the roles of PRMT5. Luciferase reporter assay was used to determine the relationship among ZFAS1/miR-150-5p/PRMT5.

Results:
Our results showed that PRMT5 was overexpressed in PCa samples. PRMT5 significantly promoted androgen-dependent PCa proliferation and cell cycle progression and suppressed cell apoptosis. However, PRMT5 did not affect androgen-independent PCa proliferation but it could significantly induce androgen-independent PCa metastasis. Knockdown of PRMT5 suppressed, whereas overexpression of PRMT5 induced, cell migration and invasion in androgen-independent DU145 and PC-3 cells. Moreover, our results showed that the ZFAS1/miR-150-5p axis regulated PRMT5 expression in PCa cells. Furthermore, the study showed that ZFAS1 and PRMT5 were overexpressed and miR-150-5p was down-regulated in PCa samples. Higher expression levels of ZFAS1 and PRMT5 were correlated with shorter disease-free survival time in PCa patients.

Conclusions:
These results showed that PRMT5 may be a therapeutic target for PCa.

eISSN:1896-9151
ISSN:1734-1922