Browse > Article
http://dx.doi.org/10.14348/molcells.2015.2146

MicroRNA-576-3p Inhibits Proliferation in Bladder Cancer Cells by Targeting Cyclin D1  

Liang, Zhen (Department of Urology, the First Affiliated Hospital, Zhejiang University)
Li, Shiqi (Department of Urology, the First Affiliated Hospital, Zhejiang University)
Xu, Xin (Department of Urology, the First Affiliated Hospital, Zhejiang University)
Xu, Xianglai (Department of Urology, the First Affiliated Hospital, Zhejiang University)
Wang, Xiao (Department of Urology, the First Affiliated Hospital, Zhejiang University)
Wu, Jian (Department of Urology, the First Affiliated Hospital, Zhejiang University)
Zhu, Yi (Department of Urology, the First Affiliated Hospital, Zhejiang University)
Hu, Zhenghui (Department of Urology, the First Affiliated Hospital, Zhejiang University)
Lin, Yiwei (Department of Urology, the First Affiliated Hospital, Zhejiang University)
Mao, Yeqing (Department of Urology, the First Affiliated Hospital, Zhejiang University)
Chen, Hong (Department of Urology, the First Affiliated Hospital, Zhejiang University)
Luo, Jindan (Department of Urology, the First Affiliated Hospital, Zhejiang University)
Liu, Ben (Department of Urology, the First Affiliated Hospital, Zhejiang University)
Zheng, Xiangyi (Department of Urology, the First Affiliated Hospital, Zhejiang University)
Xie, Liping (Department of Urology, the First Affiliated Hospital, Zhejiang University)
Publication Information
Molecules and Cells / v.38, no.2, 2015 , pp. 130-137 More about this Journal
Abstract
MicroRNAs (miRNAs) are small, endogenous RNAs that play important gene-regulatory roles by binding to the imperfectly complementary sequences at the 3'-UTR of mRNAs and directing their gene expression. Here, we first discovered that miR-576-3p was down-regulated in human bladder cancer cell lines compared with the non-malignant cell line. To better characterize the role of miR-576-3p in bladder cancer cells, we over-expressed or down-regulated miR-576-3p in bladder cancer cells by transfecting with chemically synthesized mimic or inhibitor. The overexpression of miR-576-3p remarkably inhibited cell proliferation via G1-phase arrest, and decreased both mRNA and protein levels of cyclin D1 which played a key role in G1/S phase transition. The knock-down of miR-576-3p significantly promoted the proliferation of bladder cancer cells by accelerating the progression of cell cycle and increased the expression of cyclin D1. Moreover, the dual-luciferase reporter assays indicated that miR-576-3p could directly target cyclin D1 through binding its 3'-UTR. All the results demonstrated that miR-576-3p might be a novel suppressor of bladder cancer cell proliferation through targeting cyclin D1.
Keywords
bladder cancer; cyclin D1; microRNA-576-3p; proliferation;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Allegra, A., Alonci, A., Campo, S., Penna, G., Petrungaro, A., Gerace, D., and Musolino, C. (2012). Circulating microRNAs: new biomarkers in diagnosis, prognosis and treatment of cancer (review). Int. J. Oncol. 41, 1897-1912.   DOI
2 Bartel, D.P. (2009). MicroRNAs: target recognition and regulatory functions. Cell 136, 215-233.   DOI   ScienceOn
3 Catto, J.W., Alcaraz, A., Bjartell, A.S., De Vere White, R., Evans, C.P., Fussel, S., Hamdy, F.C., Kallioniemi, O., Mengual, L., Schlomm, T., et al. (2011). MicroRNA in prostate, bladder, and kidney cancer: a systematic review. Eur. Urol. 59, 671-681.   DOI   ScienceOn
4 Chen, J., Feilotter, H.E., Pare, G.C., Zhang, X., Pemberton, J.G., Garady, C., Lai, D., Yang, X., and Tron, V.A. (2010). MicroRNA- 193b represses cell proliferation and regulates cyclin D1 in melanoma. Am. J. Pathol. 176, 2520-2529.   DOI   ScienceOn
5 Cho, W.C. (2010). MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int. J. Biochem. Cell Biol. 42, 1273-1281.   DOI   ScienceOn
6 Coskun, E., Neumann, M., Schlee, C., Liebertz, F., Heesch, S., Goekbuget, N., Hoelzer, D., and Baldus, C.D. (2013). MicroRNA profiling reveals aberrant microRNA expression in adult ETPALL and functional studies implicate a role for miR-222 in acute leukemia. Leuk. Res. 37, 647-656.   DOI   ScienceOn
7 Fang, Y., Cao, Z., Hou, Q., Ma, C., Yao, C., Li, J., Wu, X.R., and Huang, C. (2013). Cyclin d1 downregulation contributes to anticancer effect of isorhapontigenin on human bladder cancer cells. Mol. Cancer Ther. 12, 1492-1503.   DOI   ScienceOn
8 Fendler, A., Stephan, C., Yousef, G.M., and Jung, K. (2011). MicroRNAs as regulators of signal transduction in urological tumors. Clin. Chem. 57, 954-968.   DOI   ScienceOn
9 Friedman, R.C., Farh, K.K., Burge, C.B., and Bartel, D.P. (2009). Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19, 92-105.
10 Fu, M., Wang, C., Li, Z., Sakamaki, T., and Pestell, R.G. (2004). Minireview: Cyclin D1: normal and abnormal functions. Endocrinology 145, 5439-5447.   DOI   ScienceOn
11 Jemal, A., Bray, F., Center, M.M., Ferlay, J., Ward, E., and Forman, D. (2011). Global cancer statistics. CA Cancer J. Clin. 61, 69-90.   DOI
12 Kim, J.K., and Diehl, J.A. (2009). Nuclear cyclin D1: an oncogenic driver in human cancer. J. Cell. Physiol. 220, 292-296.   DOI   ScienceOn
13 Kopparapu, P.K., Boorjian, S.A., Robinson, B.D., Downes, M., Gudas, L.J., Mongan, N.P., and Persson, J.L. (2013). Expression of cyclin d1 and its association with disease characteristics in bladder cancer. Anticancer Res. 33, 5235-5242.
14 Lin, Y., Chen, H., Hu, Z., Mao, Y., Xu, X., Zhu, Y., Xu, X., Wu, J., Li, S., Mao, Q., et al. (2013). miR-26a inhibits proliferation and motility in bladder cancer by targeting HMGA1. FEBS Lett. 587, 2467-2473.   DOI   ScienceOn
15 Li, S., Xu, X., Xu, X., Hu, Z., Wu, J., Zhu, Y., Chen, H., Mao, Y., Lin, Y., Luo, J., et al. (2013). MicroRNA-490-5p inhibits proliferation of bladder cancer by targeting c-Fos. Biochem. Biophys. Res. Commun. 441, 976-981.   DOI   ScienceOn
16 Lin, T., Dong, W., Huang, J., Pan, Q., Fan, X., Zhang, C., and Huang, L. (2009). MicroRNA-143 as a tumor suppressor for bladder cancer. J. Urol. 181, 1372-1380.   DOI   ScienceOn
17 Lin, Y., Wu, J., Chen, H., Mao, Y., Liu, Y., Mao, Q., Yang, K., Zheng, X., and Xie, L. (2012). Cyclin-dependent kinase 4 is a novel target in micoRNA-195-mediated cell cycle arrest in bladder cancer cells. FEBS Lett. 586, 442-447.   DOI   ScienceOn
18 Liu, J.Y., Qian, D., He, L.R., Li, Y.H., Liao, Y.J., Mai, S.J., Tian, X.P., Liu, Y.H., Zhang, J.X., Kung, H.F., et al. (2013). PinX1 suppresses bladder urothelial carcinoma cell proliferation via the inhibition of telomerase activity and p16/cyclin D1 pathway. Mol. Cancer 12, 148.   DOI   ScienceOn
19 Majid, S., Dar, A.A., Saini, S., Deng, G., Chang, I., Greene, K., Tanaka, Y., Dahiya, R., and Yamamura, S. (2013). MicroRNA- 23b functions as a tumor suppressor by regulating Zeb1 in bladder cancer. PLoS One 8, e67686.   DOI
20 Malumbres, M., and Barbacid, M. (2009). Cell cycle, CDKs and cancer: a changing paradigm. Nat. Rev. Cancer 9, 153-166.   DOI   ScienceOn
21 Nana-Sinkam, S.P., and Croce, C.M. (2010). MicroRNA dysregulation in cancer: opportunities for the development of microRNA-based drugs. Invest. Drugs J. 13, 843-846.
22 Ploeg, M., Aben, K.K., and Kiemeney, L.A. (2009). The present and future burden of urinary bladder cancer in the world. World J. Urol. 27, 289-293.   DOI
23 Osaki, M., Takeshita, F., and Ochiya, T. (2008). MicroRNAs as biomarkers and therapeutic drugs in human cancer. Biomarkers 13, 658-670.   DOI   ScienceOn
24 Piva, R., Spandidos, D.A., and Gambari, R. (2013). From microRNA functions to microRNA therapeutics: novel targets and novel drugs in breast cancer research and treatment (Review). Int. J. Oncol. 43, 985-994.   DOI
25 Place, R.F., Li, L.C., Pookot, D., Noonan, E.J., and Dahiya, R. (2008). MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc. Natl. Acad. Sci. USA 105, 1608-1613.   DOI   ScienceOn
26 Ratert, N., Meyer, H.A., Jung, M., Lioudmer, P., Mollenkopf, H.J., Wagner, I., Miller, K., Kilic, E., Erbersdobler, A., Weikert, S., et al. (2013). miRNA profiling identifies candidate mirnas for bladder cancer diagnosis and clinical outcome. J. Mol. Diagn. 15, 695-705.   DOI   ScienceOn
27 Satyanarayana, A., and Kaldis, P. (2009). Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms. Oncogene 28, 2925-2939.   DOI   ScienceOn
28 Shi, Z., Wei, Q., Zhang, M., and She, J. (2014). MicroRNAs in bladder cancer: expression profiles, biological functions, regulation, and clinical implications. Crit. Rev. Eukaryot. Gene Expr. 24, 55-75.   DOI   ScienceOn
29 Sun, F., Fu, H., Liu, Q., Tie, Y., Zhu, J., Xing, R., Sun, Z., and Zheng, X. (2008). Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest. FEBS Lett. 582, 1564-1568.   DOI   ScienceOn
30 Tashiro, E., Tsuchiya, A., and Imoto, M. (2007). Functions of cyclin D1 as an oncogene and regulation of cyclin D1 expression. Cancer Sci. 98, 629-635.   DOI   ScienceOn
31 Zhang, Z.C., Huang, Y., Wang, X.J., Wang, M., and Ma, L.L. (2013). Expression of circulating microRNAs in patients with bladder urothelial carcinoma. Beijing Da Xue Xue Bao 45, 532-536.
32 Tatarano, S., Chiyomaru, T., Kawakami, K., Enokida, H., Yoshino, H., Hidaka, H., Yamasaki, T., Kawahara, K., Nishiyama, K., Seki, N., et al. (2011). miR-218 on the genomic loss region of chromosome 4p15.31 functions as a tumor suppressor in bladder cancer. Int. J. Oncol. 39, 13-21.
33 Witzel, II, Koh, L.F., and Perkins, N.D. (2010). Regulation of cyclin D1 gene expression. Biochem. Soc. Trans. 38, 217-222.   DOI   ScienceOn
34 Xia, H., Qi, Y., Ng, S.S., Chen, X., Chen, S., Fang, M., Li, D., Zhao, Y., Ge, R., Li, G., et al. (2009). MicroRNA-15b regulates cell cycle progression by targeting cyclins in glioma cells. Biochem. Biophys. Res. Commun. 380, 205-210.   DOI   ScienceOn