Open AccessGenetic Variation in DROSHA 3’UTR Regulated by hsa-miR-27b Is Associated with Bladder Cancer Risk
Author(s) -
Yuan Lin,
Haiyan Chu,
Meilin Wang,
Xiaoqing Gu,
Danni Shi,
Li Ma,
Dongyan Zhong,
Mulong Du,
Pu Li,
Na Tong,
Guangbo Fu,
Chao Qin,
Yin Chen,
Zhengdong Zhang
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0081524
Subject(s) - drosha , dicer , microrna , bladder cancer , single nucleotide polymorphism , genotype , three prime untranslated region , biology , untranslated region , ribonuclease iii , cancer research , genetics , gene , microbiology and biotechnology , oncology , cancer , medicine , messenger rna , rna interference , rna
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.