Abstract
ObjectVariants of microRNA (miRNA)-binding sites in RAD51 gene’s 3′ untranslated region (3′UTR) are significantly associated with cancer risk, but the roles of these genetic variants in post-transcriptional regulation have not been elucidated.MethodsThe SNPs of RAD51 were identified both in the regulatory region and in the coding region by means of the online database. The bioinformatic tool SNP Function Prediction was used to predict the potential functional relevance of the miRNA-binding sites. We used additional data on RAD51 genotypes and mRNA levels available online for the genotype-phenotype association analysis.ResultsWe found that rs12593359, rs7180135, rs11855560, and rs45507396 in the RAD51 3′UTR affect possible miRNA-binding sites according to bioinformatic analysis. Only rs12593359 was significantly associated with RAD51 mRNA expression in lymphoblastoid cell lines (P = 0.022).ConclusionThis study demonstrated that rs12593359 may be a putative variant mediating the post-transcriptional regulation of the RAD51 gene. Deeper understanding of how 3′UTR variants influence RAD51 activity will pave the way to targeting of the RAD51 pathway as a cancer treatment.
Highlights
Cancer is a common fatal disease and results from complex interactions between environmental and genetic factors (Pharoah et al 2004)
Selected variants of RAD51 3′ untranslated region (3′UTR) and putative miRNA‐binding sites In total, 849 single nucleotide polymorphisms (SNPs) were identified in the RAD51 gene region, and 38 in the mRNA-coding region
24 SNPs are located in the 3′UTR, and only 4 SNPs of these have a known minor allele frequency (MAF) value >0.05
Summary
Cancer is a common fatal disease and results from complex interactions between environmental and genetic factors (Pharoah et al 2004). More and more studies have been focused on the role of gene polymorphisms in the etiology of cancers. There is growing evidence that single nucleotide polymorphisms (SNPs) play an important role in carcinogenesis (Zeljic et al 2014; Vispé et al 1998). Deficiencies in DNA repair pathways may leave such lesions unrepaired or repaired incorrectly, The RAD51 gene is located in chromosomal region 15q15.1 in humans (Shinohara et al 1993). Growing evidence indicates that RAD51 performs an irreplaceable function in the maintenance of genomic stability and in the repair of DNA doublestrand breaks (Baumann and West 1998). A variety of molecular epidemiological studies have been conducted to estimate the association between the RAD51 135G/C polymorphism and risk of
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