Genetic variation in DROSHA 3'UTR regulated by hsa-miR-27b is associated with bladder cancer risk

PLoS One. 2013 Nov 28;8(11):e81524. doi: 10.1371/journal.pone.0081524. eCollection 2013.

Abstract

Purpose: miRNAs can regulate the biological processes, including differentiation, proliferation and apoptosis. DICER and DROSHA are two members of RNase III family, playing pivotal roles in the pathway of miRNAs biogenesis. In this study, we hypothesized that genetic variations of the DICER and DROSHA genes were associated with the bladder cancer risk.

Experimental design: We performed a case-control study of 685 bladder cancer cases and 730 controls to investigate the association between the seven functional SNPs of DICER and DROSHA genes and bladder cancer risk. We then evaluated the functionality of the important SNPs.

Results: We found that rs10719T>C polymorphism located in 3' untranslated region (UTR) of DROSHA gene was associated with the increased risk of bladder cancer. Stratified analysis suggested that rs10719TC/CC genotype can increase risk of bladder cancer among male patients (Adjusted OR = 1.34, 95% CI = 1.05-1.70, P = 0.018), and ever smokers (1.56, 1.14-2.14, 0.006), compared with TT genotype. Furthermore, DROSHA rs10719T>C polymorphism was predicted to regulate the binding activity of hsa-miR-27a/b. Luciferase reported gene assay confirmed that rs10719 T to G substitution disrupted the binding site for hsa-miR-27b, resulting the increased levels of DROSHA protein.

Conclusions: Taken together, these findings suggested that DROSHA rs10719T>C polymorphism may be associated with bladder cancer risk in a Chinese population, and hsa-miR-27b can influence the expression of DROSHA protein by binding with 3'UTR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Aged
  • Asian People / genetics
  • Base Sequence
  • Binding Sites
  • Case-Control Studies
  • DEAD-box RNA Helicases / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Ribonuclease III / genetics*
  • Urinary Bladder Neoplasms / genetics*

Substances

  • 3' Untranslated Regions
  • MIRN27 microRNA, human
  • MicroRNAs
  • DICER1 protein, human
  • DROSHA protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases

Grants and funding

This study was partly supported by National Natural Science Foundation of China (81230068, 30901166, 81202268 and 81102089), Natural Science Foundation of Jiangsu Province (BK2011773 and BK2011775), the Key Program for Basic Research of Jiangsu Provincial Department of Education (11KJB330002, and 12KJA330002), Jiangsu Provincial Six Talent Peaks Project (2012-SWYY-028), Specialized Research Fund for the Doctoral Program of Higher Education (20123234110001), Jiangsu Provincial Graduates Innovative Project (CXZZ12_0594), the Qing-Lan Project of Jiangsu Provincial Department of Education, and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.