title: MicroRNA-218 and microRNA-520a inhibit cell proliferation by downregulating E2F2 in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is the fifth most common cancer type worldwide and the third leading cause of cancer-associated mortality. To date, its pathogenesis has remained poorly understood. Previous studies have demonstrated that deregulated microRNA (miR) participates in hepatocarcinogenesis. In the present study, miR-218 and miR-520a were observed to be downregulated in human HCC cells relative to normal hepatic cells. Overexpression of miR-218 or miR-520a inhibited cell proliferation and induced cell cycle arrest at the G0/G1 phase checkpoint. Furthermore, a dual-luciferase reporter assay identified that E2F2 was a novel direct target of miR-218 but not miR-520a in HCC. In addition, miR-218 and miR-520a were observed to negatively regulate E2F2 mRNA and protein levels. This suggested that miR-218 regulated the expression of E2F2 via directly binding to its 3'-untranslated region, whereas miR-520a affected E2F2 expression indirectly. In conclusion, these results indicated that miR-218 and miR-520a are crucial in the development of HCC via the inhibition of cell proliferation and cycle progression by downregulating E2F2.
authors: The 1st Ward of the Medical Department, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China.
authors: Ye
authors: Y
authors: Dong
authors: Department of Oncology, Guangzhou Chest Hospital, Guangzhou, Guangdong 510095, P.R. China.
authors: Jianjun
authors: J
authors: Zou
authors: Department of Oncology, Guangzhou Chest Hospital, Guangzhou, Guangdong 510095, P.R. China.
authors: San
authors: S
authors: Su
authors: Department of Oncology, Guangzhou Chest Hospital, Guangzhou, Guangdong 510095, P.R. China.
authors: Huiyi
authors: H
authors: Huang
authors: The 1st Ward of the Medical Department, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China.
authors: Yanzhen
authors: Y
authors: Deng
authors: The 1st Ward of the Medical Department, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China.
authors: Birong
authors: B
authors: Wang
authors: The 1st Ward of the Medical Department, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China.
authors: Weidong
authors: W
authors: Li
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050703:E2F2 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human; C547471:MIRN218 microRNA, human; C575048:MIRN520 microRNA, human; D035683:MicroRNAs; D008156:Luciferases