title: MicroRNA-31 functions as a tumor suppressor by regulating cell cycle and epithelial-mesenchymal transition regulatory proteins in liver cancer.
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.
authors: Lab of Oncogenomics, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Functional RNomics Research Center, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Hyung Seok
authors: HS
authors: Kim
authors: Department of Orthopedic Surgery, College of Medicine, The Catholic University of Korea, Gyeonggi-do, Korea.
authors: Kyo Sun
authors: KS
authors: Lee
authors: Lab of Oncogenomics, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Functional RNomics Research Center, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Hyun Jin
authors: HJ
authors: Bae
authors: Lab of Oncogenomics, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Functional RNomics Research Center, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Jung Woo
authors: JW
authors: Eun
authors: Lab of Oncogenomics, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Functional RNomics Research Center, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Qingyu
authors: Q
authors: Shen
authors: Lab of Oncogenomics, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Functional RNomics Research Center, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Se Jin
authors: SJ
authors: Park
authors: Lab of Oncogenomics, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Functional RNomics Research Center, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Woo Chan
authors: WC
authors: Shin
authors: Lab of Oncogenomics, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Functional RNomics Research Center, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Hee Doo
authors: HD
authors: Yang
authors: Lab of Oncogenomics, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Functional RNomics Research Center, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Mijung
authors: M
authors: Park
authors: Lab of Oncogenomics, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Functional RNomics Research Center, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Won Sang
authors: WS
authors: Park
authors: Department of Orthopedic Surgery, College of Medicine, The Catholic University of Korea, Gyeonggi-do, Korea.
authors: Yong-Koo
authors: YK
authors: Kang
authors: Lab of Oncogenomics, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Functional RNomics Research Center, The Catholic University of Korea, Seoul, Republic of Korea.|Cancer Evolution Research Center, Catholic University of Korea, Seoul, Republic of Korea.
authors: Suk Woo
authors: SW
authors: Nam
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D015331:Cohort Studies; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D012307:Risk Factors; D014162:Transfection
chemical_list: C534612:MIRN31 microRNA, human; D035683:MicroRNAs
keywords: CDK2; HDAC2; cell cycle; hepatocellular carcinoma; microRNA-31