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.

Identification of MicroRNAs as Viable Aggressiveness Biomarkers for Prostate Cancer

“…However, several miRNAs, such as miR-141, miR-375, and miR-130b, lost interest as biomarkers when performing expression analysis in the present study because there were no differences among PC risk or even prognosis. Nevertheless, when looking in literature, these are among the most highlighted miRNAs as suitable biomarkers in urine, for PC diagnosis and progression [19,21]; in plasma, for time to progression of metastatic castration-resistant PC or biomarker screening [20,23,24,59]; or even associated with an increased risk of biochemical recurrence [60]. By contrast, when studying them in the present bioinformatics analyses, these three miRNAs (miR-141, miR-375, and miR-130b) completely lost total statistical power (Figures 3 and 4).…”

“…miR-375 has been included as one of the classical miRNAs' biomarkers in PC. It has importance in several points of the disease, such as clinical T-stage and bone metastasis, distinguishing between PC patients versus controls, and even differentiating between benign prostatic hyperplasia (BPH) in urinary and serum exosomes [19][20][21]. This miRNA has been included as one of the main points for regulating proliferation, metastasis, and EMT in PC, and it has also been included with a significant down-regulation after radical prostatectomy in urine extracellular vesicles (EVs), clarified urine, and blood plasma [22].…”

Genetics of Prostate Carcinoma

“…In contrast, its overall expression (defined as both epithelial and stromal expression) strongly relates to Gleason grade (P=0.001) (105). It was recently shown that plasma levels of miR-141-3p and miR-375-3p might predict time to progression in mCRPC patients treated with docetaxel or abiraterone; their high baseline levels were significantly associated with shorter overall survival (OS) in the abiraterone and in docetaxel treated patients (106)(107)(108).…”

Regulation of Neuroendocrine-like Differentiation in Prostate Cancer by Non-Coding RNAs

“…• 12 of 42 with an  in malignancy [233]   in PCa vs BPH [263]   in PCa [264] [265]   in PCa and metastases [266]   viability, migration, invasion [264]  overrides radiation-induced cell cycle arrest [267]  associated with disease recurrence [266] --  in PCa [199]   in patients with LN metastases [269]  promotes PCa progression [270,271]   expression predicts poor survival [272]  blood: BPH vs PCa [208]  seminal plasma: disease aggressiveness [   favors progression and self-renewal [129]   correlates with early clinical failure [286]  urine: cancer cell -macrophage signalling [287]  urine: PCa vs healthy [288]  negative regulation by lncRNA TTTY15 [289]  suppresses AR via Myc [290] in NEPC tissues [194] • 12 of 42 with an  in malignancy [233]   in PCa vs BPH [263]   in PCa [264] [265]   in PCa and metastases [266]   viability, migration, invasion [264]  overrides radiation-induced cell cycle arrest [267]  associated with disease recurrence [266] --  in PCa [199]   in patients with LN metastases [269]  promotes PCa progression [270,271]   expression predicts poor survival [272]  blood: BPH vs PCa [208]  seminal plasma: disease aggressiveness [273]  plasma: disease prediction [274]  serum: PCa diagnosis [275] -  in PCa [199]   in advanced PCa [260]   in patients with LN metastases …”

“…  in PCa [199]   in patients with LN metastases [269]  promotes PCa progression [270,271]   expression predicts poor survival [272]  blood: BPH vs PCa [208]  seminal plasma: disease…”