Journal of Molecular Medicine

, Volume 90, Issue 9, pp 1069–1077 | Cite as

Yin Yang-1 suppresses differentiation of hepatocellular carcinoma cells through the downregulation of CCAAT/enhancer-binding protein alpha

  • Shengjie Zhang
  • Tingting Jiang
  • Lifeng Feng
  • Jie Sun
  • Haiqi Lu
  • Qinchuan Wang
  • Min Pan
  • Dongsheng Huang
  • Xian Wang
  • Linbo Wang
  • Hongchuan Jin
Original Article

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.

Keywords

Oncogene Cancer Carcinogenesis 

Notes

Acknowledgments

This work was supported by Program for Innovative Research Team in Zhejiang Province (grant no. 2010R50046), Natural Science Foundation of Zhejiang Province to LF (grant no. Y2110257) and Program for New Century Excellent Talents in University to HJ.

Supplementary material

109_2012_879_MOESM1_ESM.pdf (281 kb)
ESM 1(PDF 280 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Shengjie Zhang
    • 1
    • 2
  • Tingting Jiang
    • 1
  • Lifeng Feng
    • 1
  • Jie Sun
    • 1
  • Haiqi Lu
    • 1
  • Qinchuan Wang
    • 1
    • 2
  • Min Pan
    • 1
  • Dongsheng Huang
    • 3
  • Xian Wang
    • 1
  • Linbo Wang
    • 2
  • Hongchuan Jin
    • 1
  1. 1.Laboratory of Cancer Epigenetics, Key Laboratory of Biotherapy in Zhejiang Province, Biomedical Research Center, Sir Run Run Shaw Hospital, School of MedicineZhejiang UniversityHangzhouChina
  2. 2.Department of Surgical Oncology, Sir Run Run Shaw Hospital, School of MedicineZhejiang UniversityHangzhouChina
  3. 3.Department of General Surgery, Sir Run Run Shaw Hospital, School of MedicineZhejiang UniversityHangzhouChina

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