Research Papers:
MicroRNA31 functions as a tumor suppressor by regulating cell cycle and epithelialmesenchymal transition regulatory proteins in liver cancer
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Hyung Seok Kim1,2,*, Kyo Sun Lee3,*, Hyun Jin Bae1,2, Jung Woo Eun1,2, Qingyu Shen1,2, Se Jin Park1,2, Woo Chan Shin1,2, Hee Doo Yang1,2, Mijung Park1,2, Won Sang Park1,2, Yong-Koo Kang3 and Suk Woo Nam1,2,4
1 Lab of Oncogenomics, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
2 Functional RNomics Research Center, The Catholic University of Korea, Seoul, Republic of Korea
3 Department of Orthopedic Surgery, College of Medicine, The Catholic University of Korea, Gyeonggi-do, Korea
4 Cancer Evolution Research Center, Catholic University of Korea, Seoul, Republic of Korea
* These authors contributed equally to this work
Correspondence to:
Suk Woo Nam, email:
Keywords: Hepatocellular carcinoma, microRNA-31, CDK2, HDAC2, cell cycle
Received: October 01, 2014 Accepted: February 04, 2015 Published: March 10, 2015
Abstract
MicroRNA-31 (miR-31) is among the most frequently altered microRNAs in human cancers and altered expression of miR-31 has been detected in a large variety of tumor types, but the functional role of miR-31 still hold both tumor suppressive and oncogenic roles in different tumor types. MiR-31 expression was down-regulated in a large cohort of hepatocellular carcinoma (HCC) patients, and low expression of miR-31 was significantly associated with poor prognosis of HCC patients. Ectopic expression of miR-31 mimics suppressed HCC cell growth by transcriptional deregulation of cell cycle proteins. Additional study evidenced miR-31 directly to suppress HDAC2 and CDK2 expression by inhibiting mRNA translation in HCC cells. We also found that ectopic expression of miR-31 mimics reduced metastatic potential of HCC cells by selectively regulating epithelial-mesenchymal transition (EMT) regulatory proteins such as N-cadherin, E-cadherin, vimentin and fibronectin. HCC tissues derived from chemical-induced rat liver cancer models validated that miR-31 expression is significantly down-regulated, and that those cell cycle- and EMT-regulatory proteins are deregulated in rat liver cancer. Overall, we suggest that miR-31 functions as a tumor suppressor by selectively regulating cell cycle and EMT regulatory proteins in human hepatocarcinogenesis providing a novel target for the molecular treatment of liver malignancies.