干扰素诱导跨膜蛋白3诱导上皮细胞间质转化促进肝癌侵袭转移

Interferon-induced transmembrane protein 3 promotes the invasion and metastasis in hepatocellular carcinoma by inducing epithelial-mesenchymal transition

目的探讨干扰素诱导跨膜蛋白3(interferon-induced transmembrane protein 3,IFITM3)通过诱导上皮细胞间质转化对肝癌侵袭转移的影响。方法采用Western Blot对比105例肝癌患者癌与癌旁组织的IFITM3表达水平,并结合病理资料分析预后。利用Western blot和q RT-PCR观察肝癌细胞株中IFITM3的表达,选取IFITM3表达较高和较低的细胞株进行沉默和过表达,检测EMT标记物的表达,通过划痕和Transwell实验检测转染后细胞株侵袭和转移能力。结果 IFITM3在肝癌中的高表达。IFITM3的高表达与卫星灶、包膜、血管侵袭和TNM分期相关(P<0.05)。Kaplan-Meier生存分析发现IFITM3高表达的患者的总体生存率和无病生存率都要更低(P<0.001)。在体外试验中,IFITM3与细胞的侵袭、迁移能力以及上皮细胞间质化水平正相关。结论 IFITM3可以通过诱导上皮细胞间质转化促进肝癌侵袭转移。

Objective To explore the effects of Interferon-induced transmembrane protein 3 on promoting the invasion and metastasis in hepatocellular carcinoma though inducing epithelial-mesenchymal transition(EMT).Methods Western blot and IHC assays were used to investigate the difference of IFITM3 expression between HCC tissue samples and the corresponding adjacent tissues.The Kaplan-Meier and Cox regression model was used to assess the relationship of IFITM3 levels and clinicopathological variables.The expression of IFITM3 in HCC cell lines were detected by Western blot and qRT-PCR.Using the low IFITM3 expressed cell line to upregulated,and the high IFITM3 expressed cell line to downregulated.After the transfection,we investigate the relationship between IFITM3 and EMT markers by Western blot.And the invasion and metastasis changes was observed.Results IFITM3 expression was higher in HCC tissues than adjacent non-tumor tissues.High IFITM3 expression correlated with tumor microsatellite formation,tumor encapsulation,venous invasion,and tumor node metastasis(TNM)stage(P<0.05).Kaplan-Meier survival analysis demonstrated that HCC patients with high IFITM3 expression had poorer overall survival(OS;P<0.001)and disease-free survival(DFS;P<0.001).IFITM3 silencing decreased in vitro migration,invasion,and epithelial-mesenchymal transition(EMT).Conversely,IFITM3 overexpression in HCC cell lines increased in vitro migration,invasion,and EMT.Conclusion These findings show that IFITM3 promotes HCC invasion and metastasis by inducing EMT.