Circulating Microrna-23b-3p And Tissue Microrna-193a-3p As Promising Molecular Biomarkers In Human Hepatocellular Carcinoma

MicroRNAs (miRs) are small non-coding RNAs that act mainly as negative regulators of gene expression. The dysregulation of miRs is clearly implicated in cancer. Because of their release and stability in body fluids (i.e. serum and plasma), miRs have received growing attention as biomarkers in cancer, including hepatocellular carcinoma (HCC). Recently, we have demonstrated that miR-193a-3p and miR-23b-3p exert a tumor-suppressor role in HCC. Here, we shifted our attention from the biological to the potential clinical significance of miR-193a-3p and miR-23b-3p exploring their diagnostic and prognostic value in HCC. The expression levels of miR-193a-3p and -23b-3p resulted significantly down-regulated in primary HCCs compared to their matched peritumoral (PT) counterparts in a cohort of HCC patients (n=67, n=59, respectively) as indicated by stem-loop qPCR results. Interestingly, high miR-193a-3p level in HCCs was associated with longer OS and DFS of patients. It is known that the expression of miRs can be regulated by DNA methylation and the alteration of this epigenetic mark may occur in cancer. For this purpose, we verified the DNA methylation level of the CpG islands identified near the miRs coding sequences using the methylation-specific PCR. An inverse trend between miR-23b-3p (but not miR-193a-3p) expression and DNA methylation was observed in a subset of 30 HCC cases and cells. Finally, to explore the potential role of these miRs as circulating biomarkers of HCC, we used the droplet digital PCR for the detection of miR-23b-3p and miR-193a-3p in the plasma from HCC patients (n=25) and healthy subjects (n=37). The plasmatic level of miR-23b-3p was significantly lower in HCC patients respect to controls and it was associated with tumor grading; while miR-193a-3p resulted undetectable in the plasma samples. Further analyses are ongoing to investigate the potential role of circulating miR-23b-3p as a non-invasive biomarker of response to therapy in HCC patients.