论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
Authors Cai C, Zhi Y, Wang K, Zhang P, Ji Z, Xie C, Sun F
Received 4 December 2018
Accepted for publication 2 April 2019
Published 2 May 2019 Volume 2019:12 Pages 3363—3372
DOI https://doi.org/10.2147/OTT.S196931
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Ms Justinn Cochran
Peer reviewer comments 2
Editor who approved publication: Dr Federico Perche
Objective: Circular
RNA is a type of endogenous RNA molecule with a stable closed-loop structure
which is ubiquitous in mammals. Circular RNA HIPK3 (circHIPK3) is highly
expressed in hepatocellular carcinoma and promotes the growth of hepatoma
cells. However, its role in prostate cancer (PCa) has not been reported. This
study aims to explore whether circHIPK3 could affect the proliferative and
invasive potentials of PCa cells by regulating miRNA-338-3p.
Methods: Expression
levels of circHIPK3 and miRNA-338-3p in PCa tissues and cells were determined
by RT-qPCR. The regulatory effects of circHIPK3 and miRNA-338-3p on
proliferative and invasive potentials of PCa cells were evaluated by CCK-8 and
transwell assay, respectively. We verified the binding between miRNA-338-3p and
ADAM17, as well as miRNA-338-3p and circHIPK3 through dual-luciferase reporter
gene assay. Rescue experiments were conducted to clarify whether circHIPK3
affected the proliferative and invasive potentials of PCa cells by regulating
miRNA-338-3p.
Results: Expression
level of circHIPK3 in PCa tissues was remarkably higher than that of
paracancerous tissues. Knockdown of circHIPK3 inhibited the proliferative and
invasive rates of PC-3 and DU145 cells. Dual-luciferase reporter gene assay
indicated that circHIPK3 could bind to miRNA-338-3p. Moreover, miRNA-338-3p
expression was downregulated in PCa tissues. miRNA-338-3p expression was
negatively correlated with lymph node metastasis and distant metastasis.
miRNA-338-3p overexpression markedly reduced proliferative and invasive abilities
of PC-3 and DU145 cells. Furthermore, ADAM17 was confirmed to be the target
gene of miRNA-338-3p. Overexpression of ADAM17 enhanced proliferative and
invasive abilities of PC-3 and DU145 cells. Finally, rescue experiments
indicated that miRNA-338-3p knockdown in PC-3 and DU145 cells partially
reversed the regulatory effects of circHIPK3 on proliferative and invasive
potentials.
Conclusion: Overexpression
of circHIPK3 promotes the proliferative and invasive potentials of PCa cells
through sponging miRNA-338-3p to regulate ADAM17 expression, thus accelerating
the malignant progression of PCa.
Keywords: CircHIPK3,
miRNA-338-3p, ADAM17, prostate cancer