Lowered expression of microRNA-125a-5p in human hepatocellular carcinoma and up-regulation of its oncogenic targets sirtuin-7, matrix metalloproteinase-11, and c-Raf

// Nicola Coppola 1 , Giorgio de Stefano 2 , Marta Panella 3 , Lorenzo Onorato 1 , Valentina Iodice 2 , Carmine Minichini 1 , Nicola Mosca 3 , Luisa Desiato 3 , Nunzia Farella 2 , Mario Starace 1 , Giulia Liorre 2 , Nicoletta Potenza 3 , Evangelista Sagnelli 1 , Aniello Russo 3 1 Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy 2 IX Interventional Ultrasound Unit for Infectious Diseases, AORN dei Colli, P.O. Cotugno, Naples, Italy 3 Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Naples, Italy Correspondence to: Aniello Russo, email: aniello.russo@unina2.it Keywords: microRNA, gene regulation, cell proliferation, tumor, hepatocellular carcinoma Received: November 08, 2016     Accepted: February 07, 2017     Published: February 28, 2017 ABSTRACT Human microRNA-125a-5p (miR-125a) is expressed in most tissues where it downregulates the expression of membrane receptors or intracellular transductors of mitogenic signals, thus limiting cell proliferation. Expression of this miRNA generally increases with cell differentiation whereas it is downregulated in several types of tumors, such as breast, lung, ovarian, gastric, colon, and cervical cancers, neuroblastoma, medulloblastoma, glioblastoma, and retinoblastoma. In this study, we focused on hepatocellular carcinoma and used real-time quantitative PCR to measure miR-125a expression in 55 tumor biopsies and in matched adjacent non-tumor liver tissues. This analysis showed a downregulation of miR-125a in 80 % of patients, with a mean decrease of 4.7-fold. Comparison of miRNA downregulation with clinicopathological parameters of patients didn’t yield significant correlations except for serum bilirubin. We then evaluated the expression of known targets of miR-125a and found that sirtuin-7, matrix metalloproteinase-11, and c-Raf were up-regulated in tumor tissue by 2.2-, 3-, and 1.7-fold, respectively. Overall, these data support a tumor suppressor role for miR-125a and encourage further studies aimed at the comprehension of the molecular mechanisms governing its expression, eventually leading to treatments to restore its expression in tumor cells.