Research Papers:
Lowered expression of microRNA125a5p in human hepatocellular carcinoma and upregulation of its oncogenic targets sirtuin7 matrix metalloproteinase11 and cRaf
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Nicola Coppola1, Giorgio de Stefano2, Marta Panella3, Lorenzo Onorato1, Valentina Iodice2, Carmine Minichini1, Nicola Mosca3, Luisa Desiato3, Nunzia Farella2, Mario Starace1, Giulia Liorre2, Nicoletta Potenza3, Evangelista Sagnelli1, Aniello Russo3
1Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
2IX Interventional Ultrasound Unit for Infectious Diseases, AORN dei Colli, P.O. Cotugno, Naples, Italy
3Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Naples, Italy
Correspondence to:
Aniello Russo, email: [email protected]
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.