title: Upregulation of miR-146a by YY1 depletion correlates with delayed progression of prostate cancer.
abstract: Previously published studies explained that the excessive expression of miR-146a influences the prostate cancer (PCa) cells in terms of apoptosis, progression, and viability. Although miR-146a acts as a tumor suppressor, current knowledge on the molecular mechanisms that controls its expression in PCa is limited. In this study, gene set enrichment analysis (GSEA) showed negatively enriched expression of miR-146a target gene sets and positively enriched expression of gene sets suppressed by the enhancer of zeste homolog 2 (EZH2) after YY1 depletion in PCa cells. The current results demonstrated that the miR-146a levels in PCa tissues with high Gleason scores (>7) are significantly lower than those in PCa tissues with low Gleason scores (≤7), which were initially observed in the clinical specimens. An inverse relationship between YY1 and miR-146a expression was also observed. Experiments indicated the decrease in cell viability, proliferation, and promoting apoptosis after YY1 depletion, while through inhibiting miR-146a could alleviate the negative effect brought by YY1 depletion. We detected the reversed adjustment of YY1 to accommodate miR-146a transcriptions. On the basis of YY1 depletion, we determined that the expression of miR-146a increased after EZH2 knockdown. We validated the combination of YY1 and its interaction with EZH2 at the miR-146a promoter binding site, thereby prohibiting the transcriptional activity of miR-146a in PCa cells. Our results suggested that YY1 depletion repressed PCa cell viability and proliferation and induced apoptosis at least in a miR-146a-assisted manner.
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China.
authors.forename: Yeqing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Urology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China.
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Ling
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Lu
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China.
authors.forename: Shuqiu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D050986:YY1 Transcription Factor; C494698:YY1 protein, human