IFIT5在肝细胞癌中表达上调并促进肝癌细胞侵袭和迁移

Enhanced expression of interferon-induced protein with tetratricopeptide repeats 5 promotes migration and invasion of hepatocellular carcinoma cells

目的探讨干扰素诱导蛋白5(interferon-induced protein with tetratricopeptide repeats 5,IFIT5)在肝癌组织中的表达、临床意义及可能的分子机制。方法收集2013年在西安交通大学第一附属医院确诊的97例肝癌患者的肿瘤组织和癌旁组织。实时定量PCR、Western blot及免疫组化检测IFIT5在肝癌及癌旁组织中的表达水平,并分析IFIT5表达水平与临床病理指标的关系及生存率。Transwell实验检测IFIT5对HCC细胞的侵袭及迁移作用,Western blot法检测IFIT5对HCC细胞EMT的影响。结果IFIT5在肝癌组织中表达水平显著高于相应癌旁组织(P<0.05);肝癌组织IFIT5高表达与TNM分期(P=0.018)及血管侵犯(P=0.009)显著相关;高表达IFIT5患者5年生存率明显高于低表达组(P<0.05);IFIT5可显著促进HCC细胞的侵袭及迁移(P<0.05);IFIT5促进HCC细胞EMT的发生(P<0.05)。结论IFIT5在肝癌组织中表达升高,其高表达与肝癌恶性临床病理特征有关,IFIT5能够通过调控HCC细胞EMT促进其侵袭和迁移。

Objective To investigate the expression,clinical significance and possible underlying mechanism of interferon-induced protein with tetratricopeptide repeats 5(IFIT5)in human hepatocellular carcinoma(HCC).Methods Liver tumor tissues and adjacent normal tissues were harvested from 97 HCC patients diagnosed in the First Affiliated Hospital of Xi’an Jiaotong University between Jan Uary,2013 and December,2013.Real-time quantitative PCR,Western blotting and immunohistochemical assay were used to detect the IFIT5 expression level in 97 pairs of HCC tissue and para-cancerous tissues.The relationships of the expression level of IFIT5 with clinical pathological indexes and survival rate were analyzed.Its protein expression was also detected with Western blotting in various HCC cell lines and normal liver cell line.After the overexpression plasmid of IFIT5 was transfected into the HCC cell line Hep3 B(low IFIT5 expression),and IFIT5 siRNA was induced into the HCCLM3 cells(high IFIT5 expression),Transwell assay was performed to measure the effects of IFIT5 on the invasion and migration abilities of above the 2 kinds of HCC cells.The expression levels of EMT-related proteins were determined by Western blotting.Results The expression level of IFIT5 was significantly higher in HCC tissues than the adjacent normal tissues(P<0.05),and its high level was significantly associated with TNM stage(P=0.018)and vascular infiltration(P=0.009).The patients with higher IFIT5 level had a worse 5-year survival rate than those with lower level(P<0.05).Overexpression of IFIT5 significantly promoted the invasion and migration of HCC cells(P<0.05)and the EMT of HCC cells(P<0.05).Conclusion IFIT5 is up-regulated in HCC tissues,and its high expression is correlated with the malignant pathological features.IFIT5 can promote the invasion and migration of HCC cells by regulating EMT.