Collagen triple helix repeat containing 1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation and motility

Tameda,Masahiko; Sugimoto,Kazushi; Shiraki,Katsuya; Yamamoto,Norihiko; Okamoto,Ryuji; Usui,Masanobu; Ito,Masaaki; Takei,Yoshiyuki; Nobori,Tsutomu; Kojima,Takahiro; Suzuki,Hideaki; Uchida,Masako; Uchida,Kazuhiko

doi:10.3892/ijo.2014.2445

Collagen triple helix repeat containing 1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation and motility

Authors:
- Masahiko Tameda
- Kazushi Sugimoto
- Katsuya Shiraki
- Norihiko Yamamoto
- Ryuji Okamoto
- Masanobu Usui
- Masaaki Ito
- Yoshiyuki Takei
- Tsutomu Nobori
- Takahiro Kojima
- Hideaki Suzuki
- Masako Uchida
- Kazuhiko Uchida
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Affiliations: First Department of Internal Medicine, Mie University School of Medicine, Tsu 514-8507, Japan, Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu 514-8507, Japan, Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu 514-8507, Japan, Department of Molecular and Laboratory Medicine, Mie University School of Medicine, Tsu 514-8507, Japan, Department of Molecular Biological Oncology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan, Research Division, MCBI, Tsukuba 305-0035, Japan
Published online on: May 19, 2014 https://doi.org/10.3892/ijo.2014.2445
Pages: 541-548
Copyright: © Tameda et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Although several therapeutic options are available for hepatocellular carcinoma (HCC), the outcome is still very poor. One reason is the complexity of signal transduction in the pathogenesis of HCC. The aim of this study was to identify new HCC-related genes and to investigate the functions of these genes in the pathogenesis and progression of HCC. Whole genomes of 15 surgically resected HCC specimens were examined for copy number alterations with comparative genomic hybridization. Gene expression was compared between HCC and normal liver tissues. The roles of the new genes in the progression of HCC were studied using cultured cell lines. Copy number gain in chromosome 8q was detected in 53% of HCC tissues examined. The gene that coded for collagen triple helix repeat containing 1 (CTHRC1), located at chromosome 8q22.3, was overexpressed in HCC compared with normal or liver cirrhosis tissues and identified as a new HCC-related gene. CTHRC1 deletion with short hairpin RNA significantly reduced proliferation, migration and invasion of HepG2 and Huh7 cells. In addition, mRNA of integrins β-2 and β-3 was downregulated, with deletion of CTHRC1 in these cells. Immunohistochemical staining on resected HCC tissues showing positive staining areas for CTHRC1 was significantly greater in poorly-differentiated HCC compared with well‑differentiated HCC. Moreover, some cases showed strong staining for CTHRC1 in invasive areas of HCC. CTHRC1 has the potential to be a new biomarker for the aggressive HCC, and to be a new therapeutic target in treating HCC.

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