title: MiR-29a suppresses prostate cell proliferation and induces apoptosis via KDM5B protein regulation.
abstract: Small regulatory RNAs, known as microRNAs, regulate gene expression at the post-transcriptional level; such as protein translation inhibition or mRNA degradation. Altered miRNA expressions have been implicated in various cancers. In present studies, it was demonstrated that microRNA-29a (miR-29a) expressions were significantly lower in prostate cancer (PCa) patient samples, but the role of microRNA-29s in PCa remains unclear. KDM5B was highly expressed in PCa cancer cells. Bioinformatics analysis revealed a conserved target site for miR-29a in the 3-untranslated region (UTR) of KDM5B. Gain-of-function studies using mature miR-29a were performed to investigate cell proliferation and apoptosis in two PCa cell lines (LNCaP and PC-3). We utilized gene expression analysis and in silico database analysis to identify miR-29a-mediated molecular pathways and targets. We showed that miR-29a significantly suppressed the activity of a lucifarice reporter containing KDM5B-3'UTR, which was not observed in cells transfected with mutated KDM5B-3'UTR. Gene expression data demonstrated that KDM5B expression was lower in noncancerous prostatic cell WPMY-1 than in the four PCa cell lines (LNCaP, 22RV1, PC-3 and DU145). Moreover, the enforced expression of miR-29a in PC-3 and LNCaP cells inhibited proliferation, and induced apoptosis by repressing the expression of KDM5B. This study revealed that the aberrant expression of miR-29a in PCa cells regulated KDM5B expression levels associated with tumor dissemination. These findings may be utilized in developing novel therapeutic tools for PCa.
authors.affiliation: Department of Urology, Tongji Hospital, Tongji University School of Medicine Shanghai 200433, People's Republic of China.
authors.forename: Junliang
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University Shanghai 200433, People's Republic of China.
authors.forename: Xuechao
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Urology, Tongji Hospital, Tongji University School of Medicine Shanghai 200433, People's Republic of China.
authors.forename: Wu
authors.initials: W
authors.lastname: Qiang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji University School of Medicine Shanghai 200433, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University Shanghai 200433, People's Republic of China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji University School of Medicine Shanghai 200433, People's Republic of China.
authors.forename: Shengsong
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji University School of Medicine Shanghai 200433, People's Republic of China.
authors.forename: Denglong
authors.initials: D
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University Shanghai 200433, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
keywords: KDM5B; Prostate cancer; histone demethylase; human; miR-29a