title: Clinical and biological significance of miR-23b and miR-193a in human hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is the most common cancer of the liver with a very poor prognosis. The dysregulation of microRNAs (miRs) is indeed implicated in HCC onset and progression. In this study, we have evaluated the expression of miR-23b and miR-193a in a large cohort of 59 and 67 HCC patients, respectively. miR-23b and miR-193a resulted significantly down-regulated in primary HCCs compared to their matched peritumoral counterparts. Furthermore, patients with higher miR-193a expression exhibited longer OS and DFS, suggesting that miR-193a may be a molecular prognostic factor for HCC patients. Since the regulation of miRs by DNA methylation may occur in human cancers, we verified whether the down-modulation of miR-23b and miR-193a in HCC tissues could be related to DNA methylation. An inverse trend between miR-23b expression and DNA methylation was observed, indicating that miR-23b can be epigenetically regulated. By contrast, the down-regulation of miR-193a was not mediated by DNA methylation. To verify the potential role of miR-23b and miR-193a as responsive molecular targets in vitro, we used the inhibitor of DNA methylation 5-aza-dC to restore miR-23b expression level in combination with miR-193a transfection. The combined treatment led to a significant inhibition of cellular proliferation and migration. Taken together, our findings provide evidence that miR-23b and miR-193a may be molecular diagnostic and prognostic factors for HCC; furthermore, miR-23b and miR-193a are responsive molecular targets for limiting HCC cell aggressiveness in combination with the epigenetic drug 5-aza-dC. Moreover, our results provide new advances in the epigenetic regulation of these miRs in HCC.
authors.affiliation: Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Brescia, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Grossi
authors.affiliation: Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Brescia, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: Arici
authors.affiliation: Department of Clinic and Experimental Sciences, Surgical Clinic, University of Brescia, Brescia, Italy.
authors.forename: Nazario
authors.initials: N
authors.lastname: Portolani
authors.affiliation: Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Brescia, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: De Petro
authors.affiliation: Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Salvi
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D018572:Disease-Free Survival; D015536:Down-Regulation; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*
chemical_list: C546818:MIRN193 microRNA, human; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D000077209:Decitabine; D001374:Azacitidine
keywords: 5-Aza-2’-deoxycytidine; HCC; epigenetics; microRNAs; molecular targets