title: MTA1 modulated by miR-30e contributes to epithelial-to-mesenchymal transition in hepatocellular carcinoma through an ErbB2-dependent pathway.
abstract: MTA1 is a metastasis-associated protein, which is essential to epithelial-to-mesenchymal transition (EMT). However, information concerning its up- and downstream regulation is rare. We investigated its upstream regulation and downstream effector in human hepatocellular carcinoma (HCC). In total, 94 paired HCC and adjacent tissue samples were involved in the study, and the results indicated that decreased miR-30e levels were associated with increased MTA1 levels in human HCC. miR-30e exerted its regulation of MTA1 transcription by binding to its 3'-untranslated region, and was negatively associated with EMT. Furthermore, significantly higher expression of MTA1 was associated with overexpression of v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ErbB2) in human HCC, and MTA1 can promote transcription of ErbB2 by binding with histone deacetylase 2 (HDAC2) and acting as a promoter. The EMT promotion effect caused by MTA1 largely depended on ErbB2, and reducing the activity of ErbB2 can significantly attenuate EMT promotion by causing overexpression of MTA1 both in vitro and in vivo. In general, downregulation of miR-30e can increase levels of MTA1 in human HCC, and furthermore promote cell invasion and metastasis by promoting ErbB2.
authors.affiliation: Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: L
authors.initials: L
authors.lastname: Deng
authors.affiliation: Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: J
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: C
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: S
authors.initials: S
authors.lastname: Lu
authors.affiliation: Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: R
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: B
authors.initials: B
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006655:Histone Deacetylases / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators
chemical_list: D006655:Histone Deacetylases; D035683:MicroRNAs; D018719:Erb-b2 Receptor Tyrosine Kinases; D012097:Repressor Proteins; D015534:Trans-Activators; C546086:MIRN30b microRNA, human; C089320:MTA1 protein, human; C508053:ERBB2 protein, human