title: Overexpression of the transcription factor MEF2D in hepatocellular carcinoma sustains malignant character by suppressing G2-M transition genes.
abstract: The underlying molecular pathogenesis in hepatocellular carcinoma remains poorly understood. The transcription factor MEF2D promotes survival in various cell types and it seems to function as an oncogene in leukemia. However, its potential contributions to solid cancers have not been explored. In this study, we investigated MEF2D expression and function in hepatocellular carcinoma, finding that MEF2D elevation in hepatocellular carcinoma clinical specimens was associated with poor prognosis. MEF2D-positive primary hepatocellular carcinoma cells displayed a faster proliferation rate compared with MEF2D-negative cells, and silencing or promoting MEF2D expression in these settings limited or accelerated cell proliferation, respectively. Notably, MEF2D-silencing abolished hepatocellular carcinoma tumorigenicity in mouse xenograft models. Mechanistic investigations revealed that MEF2D-silencing triggered G2-M arrest in a manner associated with direct downregulation of the cell-cycle regulatory genes RPRM, GADD45A, GADD45B, and CDKN1A. Furthermore, we identified MEF2D as an authentic target of miR-122, the reduced expression of which in hepatocellular carcinoma may be responsible for MEF2D upregulation. Together, our results identify MEF2D as a candidate oncogene in hepatocellular carcinoma and a potential target for hepatocellular carcinoma therapy.
authors.affiliation: Authors' Affiliations: Institute of Pathology and Southwest Cancer Center; Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China; Division of Hepatology and Gene Therapy, CIMA, University of Navarra, Pamplona; and CIBERehd. Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Leina
authors.initials: L
authors.lastname: Ma
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Limei
authors.initials: L
authors.lastname: Liu
authors.forename: Guangjie
authors.initials: G
authors.lastname: Duan
authors.forename: Qingliang
authors.initials: Q
authors.lastname: Wang
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Xu
authors.forename: Feng
authors.initials: F
authors.lastname: Xia
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Shan
authors.forename: Junjie
authors.initials: J
authors.lastname: Shen
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Bie
authors.forename: Youhong
authors.initials: Y
authors.lastname: Cui
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Bian
authors.forename: Jesus
authors.initials: J
authors.lastname: Prieto
authors.forename: Matías A
authors.initials: MA
authors.lastname: Avila
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D002455:Cell Division / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D016195:G2 Phase / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D064326:MEF2 Transcription Factors / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011379:Prognosis; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D064326:MEF2 Transcription Factors; C578043:MEF2D protein, human