Identification Validation and Functional Assessment of MicroRNA Panel Associated with Prostate Cancer

Abstract

Prostate cancer is the second most frequent cancer diagnosed in men and the fifth leading cause of death worldwide In this study miRNAs have been investigated for their potential to serve as alternative molecular markers for PCa Aberrantly expressed miRNAs were identified by using GEO datasets Using pathway and disease specific analysis eight miRNAs were selected the expression and SNPs in each of these miRNA was evaluated in cases and controls Functional analysis of the differentially expressed miRNAs was performed by transfecting miRmimics/inhibitor in PC3 cell line. Based on RNA transcriptomic analysis results target genes were chosen for further validation in clinical samples The expression analysis revealed that miR21 miR100 and miR125b were significantly down regulated whereas miR125a and miR221 were upregulated in PCa patients The rs12976445 polymorphism in miR125a revealed that the frequency of homozygous CC genotype was significantly higher in cases compared to controls However an inverse association was observed for rs57095329. Based on the transcriptome analysis five target mRNAs were chosen for further validation in PCa samples The results showed SLFN11 and EEF1A1 were down-regulated and SAT1 CYR61 were up regulated in PCa The miR215p miR1005p miR125a5p miR125b5p and miR2215p may regulate the target mRNAs EEF1A1 SLFN11 SAT1 and CYR61 which in turn can regulate a number of associated genes which are involved in the regulation of proliferative signalling pathways replicative immortality angiogenesis cell death and growth suppressors Together, this may lead to an increased risk for the development and progression of PCa newline