Collagen triple helix repeat containing 1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation and motility.
Collagen triple helix repeat containing 1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation and motility.
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DOI：
10.3892/ijo.2014.2445
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发表时间：
2014-08
影响因子：
5.2
通讯作者：
Uchida K
中科院分区：
文献类型：
--
作者：
Tameda M;Sugimoto K;Shiraki K;Yamamoto N;Okamoto R;Usui M;Ito M;Takei Y;Nobori T;Kojima T;Suzuki H;Uchida M;Uchida K
虽然有几种治疗方案可用于肝细胞癌（HCC），但结果仍然很差。原因之一是HCC发病过程中信号转导的复杂性。本研究的目的是鉴定新的HCC相关基因，并探讨这些基因在HCC发病和进展中的功能。采用比较基因组杂交技术对15例手术切除的HCC标本的全基因组拷贝数变化进行了检测。比较肝细胞癌与正常肝组织的基因表达。利用培养细胞系研究了这些新基因在HCC进展中的作用。在53%的HCC组织中检测到8q染色体拷贝数增加。编码胶原蛋白三螺旋重复序列1的基因（CTHRC1）位于染色体8q22.3，在HCC中与正常或肝硬化组织相比过表达，是一个新的HCC相关基因。短发夹RNA缺失CTHRC1可显著降低HepG2和Huh7细胞的增殖、迁移和侵袭。此外，这些细胞中整合素β-2和β-3 mRNA下调，CTHRC1缺失。切除的HCC组织免疫组化染色显示，低分化HCC中CTHRC1阳性染色区明显大于高分化HCC。此外，一些病例在HCC侵袭区显示强烈的CTHRC1染色。CTHRC1有可能成为侵袭性HCC的新生物标志物，成为治疗HCC的新靶点。
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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影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
6.4
作者：
Takeichi, Takayuki;Mocevicius, Paulius;Ryschich, Eduard
通讯作者：
Ryschich, Eduard
影响因子：
3.7
作者：
Chen YL;Wang TH;Hsu HC;Yuan RH;Jeng YM
通讯作者：
Jeng YM
影响因子：
7.3
作者：
Chochi, Yasuyo;Kawauchi, Shigeto;Sasaki, Kohsuke
通讯作者：
Sasaki, Kohsuke
影响因子：
4.7
作者：
Oberyszyn, TM;Conti, CJ;Robertson, FM
通讯作者：
Robertson, FM