miRNAs Dysregulated in Human Papillomavirus-Associated Benign Prostatic Lesions and Prostate Cancer

Background/Objectives: Chronic inflammation is a critical factor in the development of prostatic diseases, including prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa). Although this is recognized as a significant risk factor, the molecular mechanisms underlying these conditions remain unclear. Studies have shown that human papillomavirus (HPV) can infect the prostatic epithelium; however, its role in prostatic pathologies is not fully understood. This study aimed to evaluate the expression profiles of miRNAs involved in inflammation, proliferation, cell cycle regulation, apoptosis, angiogenesis, migration, invasion, and metastasis in HPV-positive and HPV-negative prostatic tissues. Methods: Using bioinformatics analyses, including interactomic and functional enrichment analyses, miRNAs associated with PCa and their potential roles in key cellular processes related to tumor progression were identified. Subsequently, some of these miRNAs were selected to evaluate their expression profiles in biopsies from patients with BPH/prostatitis and PCa, including HPV-positive and HPV-negative samples. Results: Our results revealed that 67.2% of benign lesions and 93.4% of cancer samples were HPV-positive. Interactomic analysis identified 284 miRNAs associated with PCa, with key miRNAs such as let-7c, miR-21, miR-34a, miR-126, miR-18a, miR-145, miR-221, miR-106a, miR-222, and miR-143 highlighted. Dysregulated expression of miRNAs was observed in HPV-positive tissues: miR-34a, miR-143, and miR-145 were downregulated in BPH/prostatitis, while miR-221 was upregulated. In HPV-positive PCa, additional miRNAs, including let-7c, miR-126, and miR-106a, showed altered expression. Complementarily, the functional enrichment analysis revealed that these miRNAs are associated with key biological processes that are crucial to cancer, such as cell cycle regulation, apoptosis, immune response, angiogenesis, metastasis, and tumor suppressor pathways. This finding is consistent with the predicted target genes of the evaluated miRNAs and their potential roles in processes related to cancer development and progression. Conclusions: The differential expression of HPV-induced miRNAs suggests their potential as biomarkers for diagnosing, prognosing, and treating prostatic diseases. These findings offer new insights into the molecular mechanisms linking HPV to prostatic pathologies.