The Pre-miR-27a Gene Polymorphism Rs895819 and Risk of Prostate Cancer Progression

Abstract

Small single-stranded, non-coding RNA molecules known as microRNAs (miRNAs) are capable of regulating gene expression by suppressing translation or degrading mRNAs resulting in diverse consequences. MiRNAs are synthesized as an individual primary transcript or as a gene cluster and each can act alone or together to control a single gene or a network of genes. The miR-23a~27a~24-2 gene cluster are individually processed of each other and have their own unique mature miRNA expression profile in various prostate cancer cell lines. Previous studies have reported the dysregulation of mature miR-27a and corresponding gene targets to be associated with cancer. A single nucleotide polymorphism in pre-miR-27a at position 40 (chr.19p13.1, SNP rs895819 T>C) and is proposed to affect mature miR-27a biogenesis. Rs895819 has been associated with risk of various cancers in different ethnic groups, and depending on the allele may cause up-regulation or down-regulation of mature miRNAs and pose as a risk factor for cancer. The literature evaluating SNP rs895819 is not clear with respect to its effects on miRNA processing, targeting, and its associations with PCa. In this study, we focus on miRNAs -23a, -27a, and -24-2 individually and as a cluster, and in a case-only study genotyping of rs895819 in a PCa cohort from a southwest US population consisting of a mixed ancestral background. We used a TaqMan SNP assay for genotyping rs895819 (T>C) in germline DNA samples from PCa patients and cell lines. Our data suggest rs895819 is associated with higher Gleason score sum. Based on our data we plan to investigate the miR-23a~27a~24-2 gene cluster to determine mechanisms by which these microRNAs regulate epithelial plasticity pathways in PCa.