Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

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)
  • Received : 2014.06.06
  • Accepted : 2014.11.17
  • Published : 2015.02.28
Download PDF
⟨ Previous Next ⟩

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

References

  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. https://doi.org/10.3892/ijo.2012.1647
  2. Bartel, D.P. (2009). MicroRNAs: target recognition and regulatory functions. Cell 136, 215-233. https://doi.org/10.1016/j.cell.2009.01.002
  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. https://doi.org/10.1016/j.eururo.2011.01.044
  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. https://doi.org/10.2353/ajpath.2010.091061
  5. Cho, W.C. (2010). MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int. J. Biochem. Cell Biol. 42, 1273-1281. https://doi.org/10.1016/j.biocel.2009.12.014
  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. https://doi.org/10.1016/j.leukres.2013.02.019
  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. https://doi.org/10.1158/1535-7163.MCT-12-0922
  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. https://doi.org/10.1373/clinchem.2010.157727
  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. https://doi.org/10.1210/en.2004-0959
  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. https://doi.org/10.3322/caac.20107
  12. Kim, J.K., and Diehl, J.A. (2009). Nuclear cyclin D1: an oncogenic driver in human cancer. J. Cell. Physiol. 220, 292-296. https://doi.org/10.1002/jcp.21791
  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. 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. https://doi.org/10.1016/j.bbrc.2013.11.006
  15. 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. https://doi.org/10.1016/j.juro.2008.10.149
  16. 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. https://doi.org/10.1016/j.febslet.2012.01.027
  17. 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. https://doi.org/10.1016/j.febslet.2013.06.021
  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. https://doi.org/10.1186/1476-4598-12-148
  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. https://doi.org/10.1371/journal.pone.0067686
  20. Malumbres, M., and Barbacid, M. (2009). Cell cycle, CDKs and cancer: a changing paradigm. Nat. Rev. Cancer 9, 153-166. https://doi.org/10.1038/nrc2602
  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. Osaki, M., Takeshita, F., and Ochiya, T. (2008). MicroRNAs as biomarkers and therapeutic drugs in human cancer. Biomarkers 13, 658-670. https://doi.org/10.1080/13547500802646572
  23. 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. https://doi.org/10.3892/ijo.2013.2059
  24. 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. https://doi.org/10.1073/pnas.0707594105
  25. 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. https://doi.org/10.1007/s00345-009-0383-3
  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. https://doi.org/10.1016/j.jmoldx.2013.05.008
  27. Satyanarayana, A., and Kaldis, P. (2009). Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms. Oncogene 28, 2925-2939. https://doi.org/10.1038/onc.2009.170
  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. https://doi.org/10.1615/CritRevEukaryotGeneExpr.2014007798
  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. https://doi.org/10.1016/j.febslet.2008.03.057
  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. https://doi.org/10.1111/j.1349-7006.2007.00449.x
  31. 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.
  32. Witzel, II, Koh, L.F., and Perkins, N.D. (2010). Regulation of cyclin D1 gene expression. Biochem. Soc. Trans. 38, 217-222. https://doi.org/10.1042/BST0380217
  33. 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. https://doi.org/10.1016/j.bbrc.2008.12.169
  34. 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.

Cited by

  1. The role of microRNAs in bladder cancer vol.57, pp.Suppl 1, 2016, https://doi.org/10.4111/icu.2016.57.S1.S60
  2. Down-Regulation of MicroRNA-210 Confers Sensitivity towards 1’S-1’-Acetoxychavicol Acetate (ACA) in Cervical Cancer Cells by Targeting SMAD4 vol.40, pp.4, 2017, https://doi.org/10.14348/molcells.2017.2285
  3. miRNA-556-3p promotes human bladder cancer proliferation, migration and invasion by negatively regulating DAB2IP expression vol.50, pp.6, 2017, https://doi.org/10.3892/ijo.2017.3969
  4. MicroRNA-542-3p suppresses cellular proliferation of bladder cancer cells through post-transcriptionally regulating survivin vol.579, pp.2, 2016, https://doi.org/10.1016/j.gene.2015.12.048
  5. MicroRNA-101 inhibits the proliferation and invasion of bladder cancer cells via targeting c-FOS vol.14, pp.3, 2016, https://doi.org/10.3892/mmr.2016.5534
  6. c-Met and CREB1 are involved in miR-433-mediated inhibition of the epithelial–mesenchymal transition in bladder cancer by regulating Akt/GSK-3β/Snail signaling vol.7, pp.2, 2016, https://doi.org/10.1038/cddis.2015.274
  7. MicroRNA-24 upregulation inhibits proliferation, metastasis and induces apoptosis in bladder cancer cells by targeting CARMA3 vol.47, pp.4, 2015, https://doi.org/10.3892/ijo.2015.3117
  8. Differential miRNA expressions in peripheral blood mononuclear cells for diagnosis of lung cancer vol.95, pp.10, 2015, https://doi.org/10.1038/labinvest.2015.88
  9. miR-1182 inhibits growth and mediates the chemosensitivity of bladder cancer by targeting hTERT vol.470, pp.2, 2016, https://doi.org/10.1016/j.bbrc.2016.01.014
  10. Ellipticine inhibits the proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via the STAT3 pathway vol.39, pp.4, 2017, https://doi.org/10.1080/08923973.2017.1327963
  11. MET/SMAD3/SNAIL circuit mediated by miR-323a-3p is involved in regulating epithelial–mesenchymal transition progression in bladder cancer vol.8, pp.8, 2017, https://doi.org/10.1038/cddis.2017.331
  12. miR-148a-3p represses proliferation and EMT by establishing regulatory circuits between ERBB3/AKT2/c-myc and DNMT1 in bladder cancer vol.7, pp.12, 2016, https://doi.org/10.1038/cddis.2016.373
  13. MicroRNA-608 inhibits proliferation of bladder cancer via AKT/FOXO3a signaling pathway vol.16, pp.1, 2017, https://doi.org/10.1186/s12943-017-0664-1
  14. MiR-22 suppresses epithelial–mesenchymal transition in bladder cancer by inhibiting Snail and MAPK1/Slug/vimentin feedback loop vol.9, pp.2, 2018, https://doi.org/10.1038/s41419-017-0206-1
  15. MIR-300 in the imprinted DLK1-DIO3 domain suppresses the migration of bladder cancer by regulating the SP1/MMP9 pathway vol.17, pp.24, 2018, https://doi.org/10.1080/15384101.2018.1557490
  16. Novel non invasive diagnostic strategies in bladder cancer vol.89, pp.2, 2015, https://doi.org/10.15386/cjmed-534
  17. miRNA expression profiles of premalignant and malignant arsenic-induced skin lesions vol.13, pp.8, 2018, https://doi.org/10.1371/journal.pone.0202579
  18. MicroRNA-124 inhibits cell proliferation, invasion and migration by targeting CAV1 in bladder cancer vol.16, pp.4, 2015, https://doi.org/10.3892/etm.2018.6537
  19. Dual regulatory role of CCNA2 in modulating CDK6 and MET‐mediated cell‐cycle pathway and EMT progression is blocked by miR‐381‐3p in bladder cancer vol.33, pp.1, 2015, https://doi.org/10.1096/fj.201800667r
  20. Targeting of SGK1 by miR-576-3p Inhibits Lung Adenocarcinoma Migration and Invasion vol.17, pp.1, 2015, https://doi.org/10.1158/1541-7786.mcr-18-0364
  21. CCND1, NOP14 and DNMT3B are involved in miR‐502‐5p–mediated inhibition of cell migration and proliferation in bladder cancer vol.53, pp.2, 2015, https://doi.org/10.1111/cpr.12751
  22. Clinical Potentials of miR-576-3p, miR-613, NDRG2 and YKL40 in Colorectal Cancer Patients vol.21, pp.6, 2020, https://doi.org/10.31557/apjcp.2020.21.6.1689
  23. Long noncoding RNA ZFPM2-AS1 promotes the proliferation, migration, and invasion of hepatocellular carcinoma cells by regulating the miR-576-3p/HIF-1α axis vol.32, pp.8, 2021, https://doi.org/10.1097/cad.0000000000001070
  24. Export Control: Post-transcriptional Regulation of the COPII Trafficking Pathway vol.8, pp.None, 2021, https://doi.org/10.3389/fcell.2020.618652