The loss of the tumour-suppressor miR-145 results in the shorter disease-free survival of prostate cancer patients

Background: Prostate cancer (PCa) is characterised by great heterogeneity of the disease progression rate. Tumours range from insignificant and not life threatening to high risk for relapse ones. Consequently, a large number of patients undergo unnecessary treatment. miR-145 is a well-documented tumour suppressor and its expression, which is regulated by the p53 pathway, has been found to be decreased in the majority of human malignancies. The aim of our study was to evaluate the clinical utility of miR-145 for the prognostication of PCa. Methods: Total RNA was isolated from 137 prostate tissue specimens obtained from 73 radical prostatectomy-treated PCa patients and 64 transurethral- or open prostatectomy-treated benign prostate hyperplasia (BPH) patients. Following polyadenylation and reverse transcription, miR-145 levels were determined by quantitative real-time PCR assay, using SNORD48 (RNU48) for normalisation purposes. Results: Downregulated miR-145 expression was found in PCa compared with BPH patients. The reduction of miR-145 expression in PCa was correlated with higher Gleason score, advanced clinical stage, larger tumour diameter and higher prostate-specific antigen (PSA) and follow-up PSA levels. In addition, higher risk for biochemical recurrence and significantly shorter disease-free survival (DFS) was found for the PCa patients expressing lower miR-145. Focusing on ‘low- and intermediate-recurrence risk’ PCa patients, miR-145 loss was revealed to be a reliable predictor of biochemical relapse and poor DFS independent from Gleason score, clinical stage, PSA and patients’ age. Conclusion: The loss of the tumour-suppressor miR-145 increases the risk for disease progression and predicts the poor survival of PCa patients

Biomarkers with prognostic potential in prostate cancer

Prostate cancer (CaP) is the most frequently diagnosed cancer among men and the second leading cause of cancer death for men in both economically developed and developing countries. CaP is usually diagnosed at an early stage with prostate biopsy, following a screening test showing elevated serum levels of prostate-specific antigen (PSA) and/or a positive digital rectal examination. Early CaP diagnosis is the main cause for the significant decrease of metastatic cases, observed during the last twenty years. On the other hand, the wide use of the PSA screening test led also to CaP overdiagnosis and overtreatment. Because of the large variation of CaP characteristics and clinicopathological features, accurate prognosis of CaP patients is a very important issue that determines treatment options. In this chapter, we review the most promising prognostic CaP biomarkers that have been suggested so far. In the emerging era of personalized medicine, these CaP biomarkers could be exploited in the clinics to increase CaP patients’ survival and quality of life. © 2018 Bentham Science Publishers

Epi-miRNAs: Modern mediators of methylation status in human cancers

Methylation of the fundamental macromolecules, DNA/RNA, and proteins, is remarkably abundant, evolutionarily conserved, and functionally significant in cellular homeostasis and normal tissue/organism development. Disrupted methylation imprinting is strongly linked to loss of the physiological equilibrium and numerous human pathologies, and most importantly to carcinogenesis, tumor heterogeneity, and cancer progression. Mounting recent evidence has documented the active implication of miRNAs in the orchestration of the multicomponent cellular methylation machineries and the deregulation of methylation profile in the epigenetic, epitranscriptomic, and epiproteomic levels during cancer onset and progression. The elucidation of such regulatory networks between the miRNome and the cellular methylation machineries has led to the emergence of a novel subclass of miRNAs, namely “epi-miRNAs” or “epi-miRs.” Herein, we have summarized the existing knowledge on the functional role of epi-miRs in the methylation dynamic landscape of human cancers and their clinical utility in modern cancer diagnostics and tailored therapeutics. This article is categorized under: RNA in Disease and Development > RNA in Disease. © 2022 Wiley Periodicals LLC