Upregulation of miR-146a by YY1 depletion correlates with delayed progression of prostate cancer

Huang,Yeqing; Tao,Tao; Liu,Chunhui; Guan,Han; Zhang,Guangyuan; Ling,Zhixin; Zhang,Lei; Lu,Kai; Chen,Shuqiu; Xu,Bin; Chen,Ming

doi:10.3892/ijo.2017.3840

Upregulation of miR-146a by YY1 depletion correlates with delayed progression of prostate cancer

Authors:
- Yeqing Huang
- Tao Tao
- Chunhui Liu
- Han Guan
- Guangyuan Zhang
- Zhixin Ling
- Lei Zhang
- Kai Lu
- Shuqiu Chen
- Bin Xu
- Ming Chen
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Affiliations: Department of Urology, Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China, Department of Urology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui, P.R. China
Published online on: January 5, 2017 https://doi.org/10.3892/ijo.2017.3840
Pages: 421-431
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	Katzenwadel A and Wolf P: Androgen deprivation of prostate cancer: Leading to a therapeutic dead end. Cancer Lett. 367:12–17. 2015. View Article : Google Scholar : PubMed/NCBI
3	Hua K, Jin J, Zhang H, Zhao B, Wu C, Xu H and Fang L: MicroRNA-7 inhibits proliferation, migration and invasion of thyroid papillary cancer cells via targeting CKS2. Int J Oncol. 49:1531–1540. 2016.PubMed/NCBI
4	Li J, Yang X, Guan H, Mizokami A, Keller ET, Xu X, Liu X, Tan J, Hu L, Lu Y, et al: Exosome-derived microRNAs contribute to prostate cancer chemoresistance. Int J Oncol. 49:838–846. 2016.PubMed/NCBI
5	Xu B, Wang N, Wang X, Tong N, Shao N, Tao J, Li P, Niu X, Feng N, Zhang L, et al: MiR-146a suppresses tumor growth and progression by targeting EGFR pathway and in a p-ERK-dependent manner in castration-resistant prostate cancer. Prostate. 72:1171–1178. 2012. View Article : Google Scholar
6	Sun Q, Zhao X, Liu X, Wang Y, Huang J, Jiang B, Chen Q and Yu J: miR-146a functions as a tumor suppressor in prostate cancer by targeting Rac1. Prostate. 74:1613–1621. 2014. View Article : Google Scholar : PubMed/NCBI
7	Xu B, Huang Y, Niu X, Tao T, Jiang L, Tong N, Chen S, Liu N, Zhu W and Chen M: Hsa-miR-146a-5p modulates androgen-independent prostate cancer cells apoptosis by targeting ROCK1. Prostate. 75:1896–1903. 2015. View Article : Google Scholar : PubMed/NCBI
8	Liu R, Yi B, Wei S, Yang WH, Hart KM, Chauhan P, Zhang W, Mao X, Liu X, Liu CG, et al: FOXP3-miR-146-NF-κB axis and therapy for precancerous lesions in prostate. Cancer Res. 75:1714–1724. 2015. View Article : Google Scholar : PubMed/NCBI
9	Bhalla SS, Robitaille L and Nemer M: Cooperative activation by GATA-4 and YY1 of the cardiac B-type natriuretic peptide promoter. J Biol Chem. 276:11439–11445. 2001. View Article : Google Scholar : PubMed/NCBI
10	Lee MY, Lu A and Gudas LJ: Transcriptional regulation of Rex1 (zfp42) in normal prostate epithelial cells and prostate cancer cells. J Cell Physiol. 224:17–27. 2010.PubMed/NCBI
11	Luo J, Zhou X, Ge X, Liu P, Cao J, Lu X, Ling Y and Zhang S: Upregulation of Ying Yang 1 (YY1) suppresses esophageal squamous cell carcinoma development through heme oxygenase-1. Cancer Sci. 104:1544–1551. 2013. View Article : Google Scholar : PubMed/NCBI
12	Xu B, Feng NH, Li PC, Tao J, Wu D, Zhang ZD, Tong N, Wang JF, Song NH, Zhang W, et al: A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate. 70:467–472. 2010. View Article : Google Scholar
13	Tao T, Wang Y, Luo H, Yao L, Wang L, Wang J, Yan W, Zhang J, Wang H, Shi Y, et al: Involvement of FOS-mediated miR-181b/miR-21 signalling in the progression of malignant gliomas. Eur J Cancer. 49:3055–3063. 2013. View Article : Google Scholar : PubMed/NCBI
14	Taganov KD, Boldin MP, Chang KJ and Baltimore D: NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA. 103:12481–12486. 2006. View Article : Google Scholar : PubMed/NCBI
15	Zhang B, Wang LL, Ren RJ, Dammer EB, Zhang YF, Huang Y, Chen SD and Wang G: MicroRNA-146a represses LRP2 translation and leads to cell apoptosis in Alzheimer's disease. FEBS Lett. 590:2190–2200. 2016. View Article : Google Scholar : PubMed/NCBI
16	Tsang DP, Wu WK, Kang W, Lee YY, Wu F, Yu Z, Xiong L, Chan AW, Tong JH, Yang W, et al: Yin Yang 1-mediated epigenetic silencing of tumour-suppressive microRNAs activates nuclear factor-κB in hepatocellular carcinoma. J Pathol. 238:651–664. 2016. View Article : Google Scholar : PubMed/NCBI
17	Seligson D, Horvath S, Huerta-Yepez S, Hanna S, Garban H, Roberts A, Shi T, Liu X, Chia D, Goodglick L, et al: Expression of transcription factor Yin Yang 1 in prostate cancer. Int J Oncol. 27:131–141. 2005.PubMed/NCBI
18	Deng Z, Cao P, Wan MM and Sui G: Yin Yang 1: A multifaceted protein beyond a transcription factor. Transcription. 1:81–84. 2010. View Article : Google Scholar
19	Thorvaldsen JL, Weaver JR and Bartolomei MS: A YY1 bridge for X inactivation. Cell. 146:11–13. 2011. View Article : Google Scholar : PubMed/NCBI
20	Caggia S, Libra M, Malaponte G and Cardile V: Modulation of YY1 and p53 expression by transforming growth factor-β3 in prostate cell lines. Cytokine. 56:403–410. 2011. View Article : Google Scholar : PubMed/NCBI
21	Sankar N, Baluchamy S, Kadeppagari RK, Singhal G, Weitzman S and Thimmapaya B: p300 provides a corepressor function by cooperating with YY1 and HDAC3 to repress c-Myc. Oncogene. 27:5717–5728. 2008. View Article : Google Scholar : PubMed/NCBI
22	Aldiri I and Vetter ML: PRC2 during vertebrate organogenesis: A complex in transition. Dev Biol. 367:91–99. 2012. View Article : Google Scholar : PubMed/NCBI
23	Xiong X, Zhang J, Liang W, Cao W, Qin S, Dai L, Ye D and Liu Z: Fuse-binding protein 1 is a target of the EZH2 inhibitor GSK343, in osteosarcoma cells. Int J Oncol. 49:623–628. 2016.PubMed/NCBI
24	Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, Ghosh D, Pienta KJ, Sewalt RG, Otte AP, et al: The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 419:624–629. 2002. View Article : Google Scholar : PubMed/NCBI
25	Bracken AP, Pasini D, Capra M, Prosperini E, Colli E and Helin K: EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J. 22:5323–5335. 2003. View Article : Google Scholar : PubMed/NCBI
26	Wen S, Tian J, Niu Y, Li L, Yeh S and Chang C: ASC-J9(®), and not Casodex or Enzalutamide, suppresses prostate cancer stem/progenitor cell invasion via altering the EZH2-STAT3 signals. Cancer Lett. 376:377–386. 2016. View Article : Google Scholar : PubMed/NCBI
27	Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, Ghosh D, Sewalt RG, Otte AP, Hayes DF, et al: EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci USA. 100:11606–11611. 2003. View Article : Google Scholar : PubMed/NCBI
28	Cao Q, Mani RS, Ateeq B, Dhanasekaran SM, Asangani IA, Prensner JR, Kim JH, Brenner JC, Jing X, Cao X, et al: Coordinated regulation of polycomb group complexes through microRNAs in cancer. Cancer Cell. 20:187–199. 2011. View Article : Google Scholar : PubMed/NCBI
29	Zhou L, Wang L, Lu L, Jiang P, Sun H and Wang H: A novel target of microRNA-29, Ring1 and YY1-binding protein (Rybp), negatively regulates skeletal myogenesis. J Biol Chem. 287:25255–25265. 2012. View Article : Google Scholar : PubMed/NCBI
30	Weng W, Wang M, Xie S, Long Y, Li F, Sun F, Yu Y and Li Z: YY1-C/EBPα-miR34a regulatory circuitry is involved in renal cell carcinoma progression. Oncol Rep. 31:1921–1927. 2014.PubMed/NCBI
31	Ren G, Zhang G, Dong Z, Liu Z, Li L, Feng Y, Su D, Zhang Y, Huang B and Lu J: Recruitment of HDAC4 by transcription factor YY1 represses HOXB13 to affect cell growth in AR-negative prostate cancers. Int J Biochem Cell Biol. 41:1094–1101. 2009. View Article : Google Scholar
32	Wang H, Garzon R, Sun H, Ladner KJ, Singh R, Dahlman J, Cheng A, Hall BM, Qualman SJ, Chandler DS, et al: NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. Cancer Cell. 14:369–381. 2008. View Article : Google Scholar : PubMed/NCBI