Genetic Variation in DROSHA 3’UTR Regulated by hsa-miR-27b Is Associated with Bladder Cancer Risk

Abstract

PurposemiRNAs 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 DesignWe 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.ResultsWe 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.ConclusionsTaken 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.

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“…It was reported that the inactivation of DROSHA caused inhibition of cell proliferation and induced apoptosis in bladder urothelial carcinoma cells (Han et al 2013), which is partly the mechanism of the effects of DROSHA on cancers. One published study found that DROSHA rs10719T>C polymorphism in 3′UTR was associated with elevated bladder cancer risk by altering the binding site of miR-27b (Yuan et al 2013). In this study, SNP rs642321 C>T in the 3′UTR of DROSHA increased osteosarcoma risk, supporting that DROSHA polymorphism played an important role in carcinogenesis.…”

Association of a Pre-miR-27a Polymorphism with Cancer Risk: an Updated Meta-analysis

“…Out of the Twenty-five, seven articles were pooled analysis, commentary and review papers (Wang et al, 2012;Yang and Burwinkel, 2012;Ma et al, 2013;Wang et al, 2013;Xu et al, 2013b;Zhong et al, 2013;Chen et al, 2014), and four reports were cancer biology experimental studies (Hirota et al, 2012;Jahid et al, 2012;Zanetti et al, 2012;Yuan et al, 2013). Three studies were excluded given that they did not include controls (Yoon et al, 2012;Xu et al, 2013a), or reported non-cancer disease (Song et al, 2013).…”

Association between the DICER rs1057035 Polymorphism and Cancer Risk: Evidence from a Meta-analysis of 1,2675 Individuals

“…There are several epidemiological case-control studies have examined the association between DICER rs1057035 polymorphism and cancer risk (Ma et al, 2012;Chen et al, 2013;Jiang et al, 2013;Liu et al, 2013;Slaby et al, 2013;Yuan et al, 2013). Though, the findings were inconclusive or even contradictory which may be attributed to ethnicity of the population, different cancer types or small size from individual studies.…”