title: MiR-124 inhibits the migration and invasion of human hepatocellular carcinoma cells by suppressing integrin αV expression.
abstract: Tumor metastasis is the major cause of cancer-related death especially in human hepatocellular carcinoma (HCC). Although microRNAs have been implicated in tumor development, the roles of miR-124 in HCC metastasis are still not well understood. We conducted functional analysis in this study to investigate miR-124. We observed that miR-124 significantly retarded the wound healing and migration of HCC SMMC-7721 and BEL-7404 cells. Further analysis indicated miR-124 directly targeting the transcriptional factor Sp1 which is an important transcription factor for the integrin αV subunit gene transcription. Co-transfection of miR-124 with the luciferase reporter containing Sp1 3' untranslated region (UTR) significantly suppressed the luciferase activities. While mutation of the binding site of miR-124 in Sp1 mRNA 3'UTR completely abrogated the suppression of miR-124. Overexpression of miR-124 resulted in robust downregulation of Sp1 and integrin αV expression at either mRNA or protein level. Ectopic expression of miR-124 in HCC dramatically repressed the wound healing and migration in vitro and tumor metastasis in mouse experiments. Our findings demonstrated that miR-124 played as an important role in regulation of integrin αV expression in HCC, and reintroduction of miR-124 might be an alternative therapeutic strategy for controlling integrin αV expression in HCC.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Key Lab of Glycoconjugate Research, Ministry of Public Health, Shanghai, PR. China.
authors.forename: Qian Qian
authors.initials: QQ
authors.lastname: Cai
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Key Lab of Glycoconjugate Research, Ministry of Public Health, Shanghai, PR. China.
authors.forename: Yi Wei
authors.initials: YW
authors.lastname: Dong
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Key Lab of Glycoconjugate Research, Ministry of Public Health, Shanghai, PR. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Key Lab of Glycoconjugate Research, Ministry of Public Health, Shanghai, PR. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Qi
authors.affiliation: Yu Ying Children's Hospital, Wenzhou Medical University, Wenzhou, PR. China.
authors.forename: Jun Xia
authors.initials: JX
authors.lastname: Guo
authors.affiliation: Yu Ying Children's Hospital, Wenzhou Medical University, Wenzhou, PR. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Key Lab of Glycoconjugate Research, Ministry of Public Health, Shanghai, PR. China.
authors.forename: Yuan Yuan
authors.initials: YY
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Key Lab of Glycoconjugate Research, Ministry of Public Health, Shanghai, PR. China.
authors.forename: Chun Yi
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Key Lab of Glycoconjugate Research, Ministry of Public Health, Shanghai, PR. China.
authors.forename: Xing Zhong
authors.initials: XZ
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039564:Integrin alphaV / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034622:RNA Interference; D016329:Sp1 Transcription Factor / Q000235:genetics
chemical_list: D039564:Integrin alphaV; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D016329:Sp1 Transcription Factor