title: Long noncoding RNA GAS5 suppresses the migration and invasion of hepatocellular carcinoma cells via miR-21.
abstract: Long noncoding RNAs (lncRNAs) are aberrantly expressed in various cancers. Although lncRNA GAS5 (growth arrest-specific transcript 5) has been characterized as a tumor suppressor in some kinds of cancer, its role and function in hepatocellular carcinoma (HCC) remain unknown. The present report demonstrates that there are lower levels of GAS5, PDCD4, and PTEN and higher levels of microRNA-21 (miR-21) in HCC tissues than in adjacent normal tissues. Moreover, the levels of GAS5 and miR-21 were correlated with the clinicopathological characteristics of HCC. HCC patients with higher levels of GAS5 or with the lower levels of miR-21 have longer survival times. There are lower levels of GAS5 and higher levels of miR-21 in HCC cell lines (Be7402, SMMC-7721, and HCCLM3) than in normal liver L-02 cells, and the levels correlate with the aggression of the HCC cell lines. Knockdown of GAS5 upregulates miR-21 levels in Bel-7402 cells (weakly aggressive); in contrast, there are opposite changes in HCCLM3 cells (highly aggressive). Moreover, GAS5 that upregulated or downregulated the expression of PDCD4 and PTEN was reversed by inhibiting or overexpressing miR-21 level in Bel-7402 and HCCLM3 cells. Then, overexpression of GAS5 suppresses the migration and invasion of HCC cells and high expression of miR-21 largely eliminates GAS5-mediated suppression of HCC cell migration and invasion. Thus, GAS5 acts as a tumor suppressor in HCCs through negative regulation of miR-21 and its targets and proteins about migration and invasion in cancer cells, which may be a target for treating HCC.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, Jiangsu, People's Republic of China.
authors.forename: Litian
authors.initials: L
authors.lastname: Hu
authors.affiliation: School of Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Ye
authors.affiliation: Institute for Digestive Endoscopy and Medical Center for Digestive Disease, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, Jiangsu, People's Republic of China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Huang
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Luo
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, Jiangsu, People's Republic of China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, Jiangsu, People's Republic of China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, Jiangsu, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China. drqzliu@hotmail.com.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China. drqzliu@hotmail.com.
authors.forename: Qizhan
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, Jiangsu, People's Republic of China. drjpzhang@hotmail.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C561567:GAS5 long non-coding RNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Hepatocellular carcinoma; Migration and invasion; lncRNA GAS5; miR-21