成都中医药大学学报2017，Vol.40Issue(2)：41-45,5.DOI:10.13593/j.cnki.51-1501/r.2017.02.041
同源异型盒基因HOXA5抑制肝癌的侵袭和迁移通过调控UBC9的表达
Homeobox Gene HOXA5 Inhibits Invasion and Metastasis of Hepatocellular Carcinoma by Regulating Expression of UBC9
摘要
Abstract
Objeetive:Through Detecting the expression of HOXA5 in human liver carcinoma;observing the changes of hepatocellular carcinoma cell line's migration and invasion ability in stable high expression HOXA5's MHCC97H.And exploring the mechanism of how HOXA5 regulate the invasion and migration of hepatocellular carcinoma,eventually to provide a new target for the molecular targeted therapy of liver cancer.Methods:Real-time quantitative PCR (qRT-PCR),western blot and immunohistochemistry were performed to detect the expression of HOXA5 gene in liver cancer tissues.The stable high expression of HOXA5 gene in hepatocellular carcinoma cell line MHCC97H was constructed,and then the changes of migration and invasion ability of MHCC97H cells were detected by wound healing assays and Transwell invasion assays.The potential target genes of HOXA5 were screened out by using CHIP-Seq,what's more,Western and blot qRT-PCR were performed to verify the relationship between HOXA5 and its target genes in the cells which stable high expression of HOXA5 gene.Results:In the fresh liver cancer tissue and the corresponding adjacent non-tumourous tissue,immunohistochemistry showed that HOXA5 was lower in liver cancer tissues than in adjacent non-tumourous tissue.Detection of qRT-PCR and Western blot showed that the expression of HOXA5 was significantly lower in liver cancer tissues than in adjacent non-tumourous tissue.In MHCC97H cells,the overexpression of HOXA5 caused cells' invasion ability decreasing.CHIP-Seq shows that HOXA5 binding to the upstream promoter region of UBC9 gene.UBC9's mRNA and protein expression were down regulated in stably high express HOXA5's MHCC97H cells.When UBC9 was overexpressed in stably expressing HOXA5's MHCC97H cells,the invasion and migration ability of hepatocellular carcinoma cells were partially recovered.Conclusions:The expression of HOXA5 in liver carcinoma was downregulation.UBC9 mediated HOXA5's inhibition affect of cancer cell's invasion and migration,which provide a new way of thinking to further elucidate the molecular mechanism of HCC invasion and metastasis,what's more our finding may demonstrate that HOXA5 as a possible target for precision treatment of hepatocellular carcinoma.关键词
HOXA5/肝癌/MHCC97H细胞/UBC9/侵袭Key words
HOXA5/Liver carcinoma/MHCC97H cell/UBC9/Invasion分类
医药卫生引用本文复制引用
陈婧,张天洪,万雪梅,蒋菁蓉,高爽,钟森..同源异型盒基因HOXA5抑制肝癌的侵袭和迁移通过调控UBC9的表达[J].成都中医药大学学报,2017,40(2):41-45,5.基金项目
国家科技部艾滋病和病毒性肝炎等重大传染病防治重大专项(2012ZX10005001) （2012ZX10005001）
