Cellular Physiology and Biochemistry (Apr 2017)

MYBL2 is a Potential Prognostic Marker that Promotes Cell Proliferation in Gallbladder Cancer

  • Hai-Bin Liang,
  • Yang Cao,
  • Qiang Ma,
  • Yi-Jun Shu,
  • Zheng Wang,
  • Fei Zhang,
  • Yuan-Yuan Ye,
  • Huai-Feng Li,
  • Shan-Shan Xiang,
  • Xiao-Ling Song,
  • Yi Xu,
  • Yi-Chi Zhang,
  • Run-Fa Bao,
  • Rui-Yan Yuan,
  • Yi-Jian Zhang,
  • Yun-Ping Hu,
  • Lin Jiang,
  • Mao-Lan Li,
  • Xu-An Wang,
  • Xiang-Song Wu,
  • Wen-Guang Wu,
  • Shuai Zhao,
  • Yong Fand,
  • Xiao-Peng Cui,
  • Yun-Shu Lu,
  • Jian Zhou,
  • Lei Zheng,
  • Wei Gong,
  • Ying-Bin Liu

DOI
https://doi.org/10.1159/000475454
Journal volume & issue
Vol. 41, no. 5
pp. 2117 – 2131

Abstract

Read online

Background: Gallbladder cancer (GBC) is an aggressive and highly lethal biliary tract malignancy, with extremely poor prognosis. In the present study, we analyzed the potential involvement of MYBL2, a member of the Myb transcription factor family, in the carcinogenesis of human GBC. Methods: MYBL2 expression levels were measured in GBC and cholecystitis tissue specimens using quantitative real-time PCR (qRT-PCR) and immunohistochemical (IHC) assays. The effects of MYBL2 on cell proliferation and DNA synthesis were evaluated using Cell Counting Kit-8 assay (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) retention assay, flow cytometry analysis, western blot, and a xenograft model of GBC cells in nude mice. Results: MYBL2 expression was increased in GBC tissues and associated with histological differentiation, tumour invasion, clinical stage and unfavourable overall survival in GBC patients. The downregulation of MYBL2 expression resulted in the inhibition of GBC cell proliferation, and DNA replication in vitro, and the growth of xenografted tumours in nude mice. Conversely, MYBL2 overexpression resulted in the opposite effects. Conclusions: MYBL2 overexpression promotes GBC cell proliferation through the regulation of the cell cycle at the S and G2/M phase transitions. Thus, MYBL2 could serve as a potential prognostic and therapeutic biomarker in GBC patients.

Keywords