title: MicroRNA-26a suppresses epithelial-mesenchymal transition in human hepatocellular carcinoma by repressing enhancer of zeste homolog 2.
abstract: BACKGROUND
  Our previous study reported that microRNA-26a (miR-26a) inhibited tumor progression by inhibiting tumor angiogenesis and intratumoral macrophage infiltration in hepatocellular carcinoma (HCC). The direct roles of miR-26a on tumor cell invasion remain poorly understood. In this study, we aim to explore the mechanism of miR-26a in modulating epithelial-mesenchymal transition (EMT) in HCC.
  
  
  METHODS
  In vitro cell morphology and cell migration were compared between the hepatoma cell lines HCCLM3 and HepG2, which were established in the previous study. Overexpression and down-regulation of miR-26a were induced in these cell lines, and Western blot and immunofluorescence assays were used to detect the expression of EMT markers. Xenograft nude mouse models were used to observe tumor growth and pulmonary metastasis. Immunohistochemical assays were conducted to study the relationships between miR-26a expression and enhancer of zeste homolog 2 (EZH2) and E-cadherin expression in human HCC samples.
  
  
  RESULTS
  Down-regulation of miR-26a in HCCLM3 and HepG2 cells resulted in an EMT-like cell morphology and high motility in vitro and increased in tumor growth and pulmonary metastasis in vivo. Through down-regulation of EZH2 expression and up-regulation of E-cadherin expression, miR-26a inhibited the EMT process in vitro and in vivo. Luciferase reporter assay showed that miR-26a directly interacted with EZH2 messenger RNA (mRNA). Furthermore, the expression of miR-26a was positively correlated with E-cadherin expression and inversely correlated with EZH2 expression in human HCC tissue.
  
  
  CONCLUSIONS
  miR-26a inhibited the EMT process in HCC by down-regulating EZH2 expression.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, People's Republic of China.
authors.forename: De-Ning
authors.initials: DN
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Zong-Tao
authors.initials: ZT
authors.lastname: Chai
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, People's Republic of China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhu
authors.affiliation: Department of Liver Surgery, Fudan University Shanghai Cancer Center, Cancer Hospital, Shanghai, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, People's Republic of China.
authors.forename: Di-Hua
authors.initials: DH
authors.lastname: Zhan
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, People's Republic of China.
authors.forename: Bo-Gen
authors.initials: BG
authors.lastname: Ye
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, People's Republic of China.
authors.forename: Cheng-Hao
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, People's Republic of China.
authors.forename: Cheng-Dong
authors.initials: CD
authors.lastname: Qin
authors.affiliation: Department of Liver Surgery, Fudan University Shanghai Cancer Center, Cancer Hospital, Shanghai, People's Republic of China.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Zhao
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, People's Republic of China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhu
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, People's Republic of China.
authors.forename: Man-Qing
authors.initials: MQ
authors.lastname: Cao
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, People's Republic of China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Gao
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, People's Republic of China.
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Sun
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. zytang88@163.com.|Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, People's Republic of China. zytang88@163.com.
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D000071221:Enhancer of Zeste Homolog 2 Protein; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
chemical_list: D015820:Cadherins; D000071221:Enhancer of Zeste Homolog 2 Protein; D035683:MicroRNAs; D063151:Polycomb Repressive Complex 2; C528163:MIRN26 microRNA, human; C498409:EZH2 protein, human