兰州大学学报（医学版）2018，Vol.44Issue(4)：1-8,8.DOI:10.13885/j.issn.1000-2812.2018.04.001
DOCK10基因在肝癌中的突变和表达分析及对肝内胆管癌细胞增殖和迁移的影响
Bioinformatics and experimental analyses reveal DOCK10 as a potential suppressor gene in liver cancer
摘要
Abstract
Objective To study the functions of DOCK genes in liver cancer progression through bioinformatic study and experimental validation. Methods The molecular evolution of DOCK family genes was analyzed by sequence alignment.Recurrent mutational patterns and expression differences of DOCK genes between cancer and normal samples in human liver cancer were figured out by mining public cancer genomic databases.We evaluated the role of DOCK10 in intrahepatic cholangiocarcinoma (ICC) cells through gain or loss of function assays in vitro experiments.Results Based on a phylogenetic analysis of seven species, the 11members of human DOCK gene family were evolutionarily conserved.Of them, DOCK2 and DOCK10 were further found to be recurrently mutated or low-expressed in liver cancer, especially in ICC, a subtype of liver cancer, through mining public cancer genomic databases, in which the loss of function of DOCK10 occurred in ICC due to the mutations or low expression.Then we further evaluated the expression and role of DOCK10in human ICC cells, showing that DOCK10 expression was significantly down-regulated in 16 ICC specimens, as compared with the matched adjacent non-cancerous livers.Furthermore, in ICC cell lines QBC939, RBE, Hucct1, Hccc9810 and HIBEC, the silence of DOCK10 via RNA interference could promote cell proliferation and cell metastasis in vitro.Conclusions DOCK10 may function as a potential tumor suppressor gene in human ICC, where the down-regulation or mutations of DOCK10 can promote ICC progression.关键词
肝癌/肝内胆管细胞癌/胞质分裂贡献者/抑癌基因/基因突变/细胞增殖/细胞迁移Key words
liver cancer/intrahepatic cholangio cellular carcinoma/dedicator of cytokinesis/antioncogene/gene mutation/cell proliferation/cell migration分类
医药卫生引用本文复制引用
张文君,杨红,胡涛涛,韩泽广..DOCK10基因在肝癌中的突变和表达分析及对肝内胆管癌细胞增殖和迁移的影响[J].兰州大学学报（医学版）,2018,44(4):1-8,8.基金项目
国家自然科学基金项目(81472621 （）
81272271) （）
国家传染病重大专项(2012ZX10002012-008 （）
2013ZX10002010-006) （）
