含HECT和锚蛋白结构域的E3泛素化连接酶-1在肝癌中表达的意义及其对肝癌细胞增殖、侵袭能力的影响

Significance of HECT and ankyrin domain containing E3 ubiquitin ligase 1 in hepatocellular carcinoma and its effects on proliferation and invasion of tumor cells

目的 观察含HECT和锚蛋白结构域的E3泛素化连接酶-1（HACE1）在肝癌中的表达水平与预后的关系及其对肝癌细胞增殖、侵袭能力的影响.方法 免疫组织化学检测100例肝癌和癌旁组织HACE1的表达,Kaplan-Meier和Log-rank分析HACE1表达水平与患者预后的关系;利用脂质体质粒转染建立Huh7-HACE1细胞株,通过细胞计数试剂盒（CCK-8）观察HACE1过表达对Huh7细胞增殖的影响,应用Transwell检测HACE1过表达对Huh7细胞侵袭能力的影响.结果 肝癌组织中HACE1表达低于和高于癌旁组织的患者分别为68和32例,两者5年生存率对比（70.8％比90.3％）和5年复发率对比（59.7％比30.6％）差异有统计学意义（P＜0.01）.细胞增殖实验结果显示4d后Huh7-HACE1组吸光度（A）值显著低于对照组（P＜0.05）;Transwell结果显示Huh7-HACE1组侵袭能力显著低于对照组（P＜0.05）.结论 HACE1基因在肝癌组织表达水平显著低于癌旁组织,其表达水平与肝癌预后相关;过表达HACE1可抑制肝癌Huh7细胞的增殖和侵袭能力.该基因可能在肝细胞肝癌的发生发展中起重要作用.

Objective To investigate the expression of HECT and Ankyrin domain containing E3 ubiquitin ligase 1 （HACE1） in hepatocellular carcinoma （HCC） and its effect on proliferation and invasion of tumor cells.Methods HACE1 expression was measured in HCC tumors,and peritumoral tissues by immunohistochemistry from 100 patients.Prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests.The Huh7-HACE1 cell line was established using plasmid vector.The cell counting Kit-8 （CCK-8） assay and Transwell were used to observe the influence of HACE1 overexpression on proliferation and invasion of Huh7 cells respectively.Results The low and high expression of HACE1 in HCC was observed in 68 and 32 patients respectively,and there was significant difference between them in 5-year survival rate （70.8% vs.90.3%） and recurrence rate （59.7% vs.30.6%） （P 〈0.01）.The results of CCK-8 assay showed that the A value in the Huh7-HACE1 group was significantly lower than in the control group after 4 days （P 〈 0.05）.The Transwell results showed that the invasive ability in the Huh7-HACE1 group was significantly reduced as compared with the control group （P 〈 0.05）.Conclusion The expression level of HACE1 gene in HCC tissues was significantly lower than that in adjacent tissues,which was associated with the prognosis of patients.Overexpression of HACE1 could inhibit the proliferation and invasion of Huh7 cells.This gene may play an important role in carcinogenesis of HCC.