title: Yin Yang-1 suppresses differentiation of hepatocellular carcinoma cells through the downregulation of CCAAT/enhancer-binding protein alpha.
abstract: As a member of the GLI-Kruppel family of transcriptional factors, Yin Yang-1 (YY1) functions as an oncogene in various types of cancers. However, the role of YY1 in hepatocellular carcinogenesis remains unknown. In this report, we investigated the relevance of YY1 to hepatocellular carcinoma (HCC) development. We found that YY1 was upregulated in HCC cell lines. Ectopic YY1 expression promoted the growth of non-tumor liver cells that expressed low level of YY1. In contrast, YY1 depletion inhibited the growth of HCC cells which was accompanied with distinct morphological changes. Moreover, the phenotypic changes induced by YY1 depletion were attributed to cellular differentiation rather than cellular senescence. CCAAT/enhancer-binding protein alpha (CEBPA) which was important to regulate differentiation of hepatocytes was found as the direct target downregulated by YY1. Restoration of CEBPA in YY1-expressing HCC cells induced cellular differentiation and growth inhibition while knockdown of CEBPA expression in non-tumor liver cells promoted cell growth. In summary, our study demonstrated that YY1 could promote hepatocellular carcinogenesis and inhibit cellular differentiation through the downregulation of CEBPA expression.
authors.affiliation: Laboratory of Cancer Epigenetics, Key Laboratory of Biotherapy in Zhejiang Province, Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Zhang
authors.forename: Tingting
authors.initials: T
authors.lastname: Jiang
authors.forename: Lifeng
authors.initials: L
authors.lastname: Feng
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.forename: Haiqi
authors.initials: H
authors.lastname: Lu
authors.forename: Qinchuan
authors.initials: Q
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Pan
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Huang
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.forename: Linbo
authors.initials: L
authors.lastname: Wang
authors.forename: Hongchuan
authors.initials: H
authors.lastname: Jin
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015536:Down-Regulation; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000166:cytology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D050986:YY1 Transcription Factor