ZHX1 Promotes the Proliferation, Migration and Invasion of Cholangiocarcinoma Cells

PLoS One. 2016 Nov 11;11(11):e0165516. doi: 10.1371/journal.pone.0165516. eCollection 2016.


Zinc-fingers and homeoboxes 1 (ZHX1) is a transcription repressor that has been associated with the progressions of hepatocellular carcinoma, gastric cancer, and breast cancer. However, the functional roles of ZHX1 in cholangiocarcinoma (CCA) have not been determined. We investigated the expression and roles of ZHX1 during the proliferation, migration, and invasion of CCA cells. In silico analysis and immunohistochemical studies showed amplification and overexpression of ZHX1 in CCA tissues. Furthermore, ZHX1 knockdown using specific siRNAs decreased CCA cell proliferation, migration, and invasion, whereas ZHX1 overexpression promoted all three characteristics. In addition, results suggested EGR1 might partially mediate the effect of ZHX1 on the proliferation of CCA cells. Taken together, these results show ZHX1 promotes CCA cell proliferation, migration, and invasion, and present ZHX1 as a potential target for the treatment of CCA.

MeSH terms

  • Bile Duct Neoplasms / genetics*
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic / metabolism
  • Bile Ducts, Intrahepatic / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / pathology
  • Collagen / chemistry
  • Diffusion Chambers, Culture
  • Drug Combinations
  • Early Growth Response Protein 1 / genetics*
  • Early Growth Response Protein 1 / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Homeodomain Proteins / antagonists & inhibitors
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Laminin / chemistry
  • Proteoglycans / chemistry
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Drug Combinations
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Homeodomain Proteins
  • Laminin
  • Proteoglycans
  • RNA, Small Interfering
  • Transcription Factors
  • ZHX1 protein, human
  • matrigel
  • Collagen

Grant support

This work was supported by the Medical Research Center (MRC) Program (#NRF-2015R1A5A2009656) and Basic Science Research Foundation (#NRF-2015R1A1A3A04001322) of the National Research Foundation (NRF) funded by the Korean government (MEST), and by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (#0920050). We would like to thank TCGA group providing Cancer Genome Atlas (TCGA) database and tools for data analysis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.