Abstract
Background & objectives Overcoming the challenge of early diagnosis of prostate cancer (PCa) by exploring molecular biomarkers is urgently needed. With this objective, this study was designed to explore the biomarker and therapeutic potential of miRNA (miR)-363-3p in PCa pathogenesis. Methods Total participants (n=188) were enrolled, and blood and tissue samples were collected from individuals categorized into the control group (n=55), benign prostate hyperplasia (BPH) group (n=60), PCa group (n=48), and castration-resistant PCa (CRPC) group (n=25). MiR expression profiling was carried out using quantitative polymerase chain reaction (qPCR), and biomarker analysis was conducted employing receiver operating characteristics (ROC) curve. The miR-363 target genes were predicted by in silico tools like Target Scan and starBasev 2.0 and its expression was validated by qPCR and association among them was established by using the STRING database. Results The results showed that the tumour-suppressive nature of miR-363-3p in both PCa tissues and serum were significantly higher than the control with a greater area under curve (AUC) was 0.969 (sensitivity: 85%; specificity 100%) and 0.988 (sensitivity: 97.5%; specificity: 87.5%), respectively. The targetome analysis of miR-363-3p revealed five target genes-NRAS, E2F3, PTEN, MDM2, and CCNE2 which were strongly associated with cell division and proliferation. The expression analysis of the target genes showed a significant tumour-suppression of PTEN gene and significant upregulation of oncogenic genes such as NRAS, E2F3, MDM2, and CCNE2. Interpretation & conclusions Collectively, the findings of this study suggest that miR-363-3p may be a potential biomarker in differentiating individuals with PCa and CRPC from healthy controls. The miR-363-3p triggers various oncogenic genes (MDM2, NRAS, E2F3, CCNE2) and tumour suppressor genes (PTEN) that are actively involved in PCa progression and development.
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