Mir-93/mir-375: Diagnostic potential, aggressiveness correlation and common target genes in prostate cancer

Abstract

Dysregulation of miRNAs has a fundamental role in the initiation, development and progression of prostate cancer (PCa). The potential of miRNA in gene therapy and diagnostic applications is well documented. To further improve miRNAs’ ability to distinguish between PCa and benign prostatic hyperplasia (BPH) patients, nine miRNA (-21,-27b,-93,-141,-205,-221,-182,-375 and let-7a) with the highest reported differentiation power were chosen and for the first time used in comparative studies of serum and prostate tissue samples. Spearman correlations and response operating characteristic (ROC) analyses were applied to assess the capability of the miRNAs present in serum to discriminate between PCa and BPH patients. The present study clearly demonstrates that miR-93 and miR-375 could be taken into consideration as single blood-based non-invasive molecules to distinguish PCa from BPH patients. We indicate that these two miRNAs have six common, PCa-related, target genes (CCND2, MAP3K2, MXI1, PAFAH1B1, YOD1, ZFYVE26) that share the molecular function of protein binding (GO:0005515 term). A high diagnostic value of the new serum derived miR-182 (AUC = 0.881, 95% confidence interval, CI = 0.816–0.946, p < 0.0001, sensitivity and specificity were 85% and 79%, respectively) is also described.