ZHX1 Promotes the Proliferation, Migration and Invasion of Cholangiocarcinoma Cells

Ryuk-Jun Kwon; Myoung-Eun Han; Ji-Young Kim; Liangwen Liu; Yun-Hak Kim; Jin-Sup Jung; Sae-Ock Oh

doi:10.1371/journal.pone.0165516

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.

Authors

Ryuk-Jun Kwon^{1

2}, Myoung-Eun Han^{1

2}, Ji-Young Kim^{1

2}, Liangwen Liu^{1

2}, Yun-Hak Kim^{1

2}, Jin-Sup Jung³, Sae-Ock Oh^{1

2}

Affiliations

¹ Department of Anatomy, School of Medicine, Pusan National University, Busandaehak-ro 49, Mulgeum-eup, Yangsan, 50612, Republic of Korea.
² Gene & Therapy Research Center for Vessel-associated Diseases, Pusan National University, Busandaehak-ro 49, Mulgeum-eup, Yangsan, 50612, Republic of Korea.
³ Department of Physiology, School of Medicine, Pusan National University, Busandaehak-ro 49, Mulgeum-eup, Yangsan, 50612, Republic of Korea.

Abstract

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

Substances

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

Grants and funding

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.