Skip to main content

Advertisement

Log in

Hsa-miR-1 downregulates long non-coding RNA urothelial cancer associated 1 in bladder cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

MicroRNAs (miRNAs) are known to mainly target protein-coding genes at post-transcriptional level, resulting in mRNA destabilization and/or translational repression. Long non-coding RNAs (lncRNAs) are emerging as a novel set of targets for miRNAs. Here, we report that downregulated hsa-miR-1 and upregulated lncRNA urothelial cancer associated 1 (UCA1) were inversely expressed in bladder cancer. Hsa-miR-1 decreased the expression of UCA1 in bladder cancer cells in an Ago2-slicer-dependent manner. The binding site between UCA1 and hsa-miR-1 was confirmed. Overexpression of hsa-miR-1 inhibited bladder cancer cell growth, induced apoptosis, and decreased cell motility. Knockdown of UCA1 expression phenocopied the effects of upregulation of hsa-miR-1. Transfection of UCA1 expression vector partly reversed the changes caused by transfection of pre-miR-1 plasmids. This study provides evidence for hsa-miR-1 to play tumor suppressive roles via downregulating lncRNA UCA1 in bladder cancer, which may have potential therapeutic significance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.

    Article  PubMed  Google Scholar 

  2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30. doi:10.3322/caac.21166.

    Article  PubMed  Google Scholar 

  3. Kim WJ, Bae SC. Molecular biomarkers in urothelial bladder cancer. Cancer Sci. 2008;99(4):646–52. doi:10.1111/j.1349-7006.2008.00735.x.

    Article  CAS  PubMed  Google Scholar 

  4. Jones-Rhoades MW, Bartel DP, Bartel B. MicroRNAS and their regulatory roles in plants. Annu Rev Plant Biol. 2006;57:19–53. doi:10.1146/annurev.arplant.57.032905.105218.

    Article  CAS  PubMed  Google Scholar 

  5. Wu L, Fan J, Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci U S A. 2006;103(11):4034–9. doi:10.1073/pnas.0510928103.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010;466(7308):835–40. doi:10.1038/nature09267.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433(7027):769–73. doi:10.1038/nature03315.

    Article  CAS  PubMed  Google Scholar 

  8. Paraskevopoulou MD, Georgakilas G, Kostoulas N, Reczko M, Maragkakis M, Dalamagas TM, et al. DIANA-LncBase: experimentally verified and computationally predicted microRNA targets on long non-coding RNAs. Nucleic Acids Res. 2013;41(Database issue):D239–45. doi:10.1093/nar/gks1246.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Han Y, Liu Y, Gui Y, Cai Z. Long intergenic non-coding RNA TUG1 is overexpressed in urothelial carcinoma of the bladder. J Surg Oncol. 2013;107(5):555–9. doi:10.1002/jso.23264.

    Article  CAS  PubMed  Google Scholar 

  10. Han Y, Liu Y, Nie L, Gui Y, Cai Z. Inducing cell proliferation inhibition, apoptosis, and motility reduction by silencing long noncoding ribonucleic acid metastasis-associated lung adenocarcinoma transcript 1 in urothelial carcinoma of the bladder. Urology. 2013;81(1):209 e1–7. doi:10.1016/j.urology.2012.08.044.

    Article  PubMed  Google Scholar 

  11. Wang XS, Zhang Z, Wang HC, Cai JL, Xu QW, Li MQ, et al. Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma. Clin Cancer Res. 2006;12(16):4851–8. doi:10.1158/1078-0432.ccr-06-0134.

    Article  CAS  PubMed  Google Scholar 

  12. Han Y, Chen J, Zhao X, Liang C, Wang Y, Sun L, et al. MicroRNA expression signatures of bladder cancer revealed by deep sequencing. PLoS ONE. 2011;6(3):e18286. doi:10.1371/journal.pone.0018286.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Han Y, Liu Y, Zhang H, Wang T, Diao R, Jiang Z, et al. Hsa-miR-125b suppresses bladder cancer development by down-regulating oncogene SIRT7 and oncogenic long non-coding RNA MALAT1. FEBS Lett. 2013;587(23):3875–82.

    Article  CAS  PubMed  Google Scholar 

  14. Qi HH, Ongusaha PP, Myllyharju J, Cheng D, Pakkanen O, Shi Y, et al. Prolyl 4-hydroxylation regulates Argonaute 2 stability. Nature. 2008;455(7211):421–4. doi:10.1038/nature07186.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. VanGuilder HD, Vrana KE, Freeman WM. Twenty-five years of quantitative PCR for gene expression analysis. Biotechniques. 2008;44(5):619–26. doi:10.2144/000112776.

    Article  CAS  PubMed  Google Scholar 

  16. Mou L, Zhang Q, Wang Y, Sun L, Li C, Huang W, et al. Identification of Ube2b as a novel target of androgen receptor in mouse sertoli cells. Biol Reprod. 2013;89(2):32. doi:10.1095/biolreprod.112.103648.

    Article  PubMed  Google Scholar 

  17. Yang X, Zhang Y, Zhang L, Mao J. Silencing alpha-fetoprotein expression induces growth arrest and apoptosis in human hepatocellular cancer cell. Cancer Lett. 2008;271(2):281–93. doi:10.1016/j.canlet.2008.06.017.

    Article  CAS  PubMed  Google Scholar 

  18. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294(5543):853–8. doi:10.1126/science.1064921.

    Article  CAS  PubMed  Google Scholar 

  19. Ambros V. The functions of animal microRNAs. Nature. 2004;431(7006):350–5. doi:10.1038/nature02871.

    Article  CAS  PubMed  Google Scholar 

  20. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.

    Article  CAS  PubMed  Google Scholar 

  21. Sontheimer EJ, Carthew RW. Molecular biology. Argonaute journeys into the heart of RISC. Science. 2004;305(5689):1409–10. doi:10.1126/science.1103076.

    Article  CAS  PubMed  Google Scholar 

  22. Kedde M, Strasser MJ, Boldajipour B, Oude Vrielink JA, Slanchev K, le Sage C, et al. RNA-binding protein Dnd1 inhibits microRNA access to target mRNA. Cell. 2007;131(7):1273–86. doi:10.1016/j.cell.2007.11.034.

    Article  CAS  PubMed  Google Scholar 

  23. Fang Z, Wu L, Wang L, Yang Y, Meng Y, Yang H. Increased expression of the long non-coding RNA UCA1 in tongue squamous cell carcinomas: a possible correlation with cancer metastasis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117(1):89–95. doi:10.1016/j.oooo.2013.09.007.

    Article  PubMed  Google Scholar 

  24. Huang J, Zhou N, Watabe K, Lu Z, Wu F, Xu M, et al. Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27 (Kip1). Cell Death Dis. 2014;5:e1008. doi:10.1038/cddis.2013.541.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Liu SP, Yang JX, Cao DY, Shen K. Identification of differentially expressed long non-coding RNAs in human ovarian cancer cells with different metastatic potentials. Cancer Biol Med. 2013;10(3):138–41. doi:10.7497/j.issn.2095-3941.2013.03.003.

    PubMed Central  CAS  PubMed  Google Scholar 

  26. Leucci E, Patella F, Waage J, Holmstrom K, Lindow M, Porse B et al. microRNA-9 targets the long non-coding RNA MALAT1 for degradation in the nucleus. Sci Rep. 2013;3:2535. doi:10.1038/srep02535.

Download references

Acknowledgments

This work was funded by grant from the Basic Research Program of Shenzhen in China (ZDSY20120615154448514).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yaoting Gui.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, T., Yuan, J., Feng, N. et al. Hsa-miR-1 downregulates long non-coding RNA urothelial cancer associated 1 in bladder cancer. Tumor Biol. 35, 10075–10084 (2014). https://doi.org/10.1007/s13277-014-2321-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2321-2

Keywords

Navigation