Oncotarget

Research Papers:

Clinical and biological significance of miR-23b and miR-193a in human hepatocellular carcinoma

Ilaria Grossi, Bruna Arici, Nazario Portolani, Giuseppina De Petro and Alessandro Salvi _

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Oncotarget. 2017; 8:6955-6969. https://doi.org/10.18632/oncotarget.14332

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Abstract

Ilaria Grossi1, Bruna Arici1, Nazario Portolani2, Giuseppina De Petro1, Alessandro Salvi1

1Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Brescia, Italy

2Department of Clinic and Experimental Sciences, Surgical Clinic, University of Brescia, Brescia, Italy

Correspondence to:

Alessandro Salvi, email: alessandro.salvi@unibs.it

Giuseppina De Petro, email: giuseppina.depetro@unibs.it

Keywords: microRNAs, epigenetics, 5-Aza-2’-deoxycytidine, HCC, molecular targets

Received: April 11, 2016    Accepted: December 16, 2016    Published: December 28, 2016

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.


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