PGC-1α调控SIRT3通路对肝细胞癌的影响

Effect of SIRT3 pathway regulated by PGC-1α on hepatocellular carcinoma

目的探讨抑癌基因第Ⅲ类组蛋白去乙酰化酶成员3(SIRT3)在过氧化物酶体增殖物受体γ共激活因子1α(PGC-1α)的调控下对肝细胞癌(hepatocellular carcinoma,HCC)的影响。方法回顾性分析22例HCC手术标本的病理学资料,用免疫组化法检测SIRT3在22例HCC组织和癌旁组织中的表达。培养肝癌细胞系HepG2细胞,利用siRNA干扰敲低PGC-1α的表达,之后采用qRT-PCR、Western blotting验证PGC-1α的表达水平,Western blotting检测SIRT3的表达水平。结果SIRT3在HCC组织中的表达量明显低于癌旁组织(P<0.05)。敲低HepG2细胞PGC-1α蛋白的表达后,SIRT3蛋白的表达下调。结论SIRT3在HCC中发挥抑制肿瘤生长的作用,在肝癌细胞系HepG2中PGC-1α表达下调可降低SIRT3的表达水平,从而影响SIRT3的抑癌功能。

Objective To investigate the effect of sirtuin 3(SIRT3)on hepatocellular carcinoma(HCC)under the regulation of peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α).Methods Immunohistochemistry was used in this study to detect the protein expression of SIRT3 in 22 HCC tissues and corresponding para-tumorous tissues from patients with HCC undergoing curative hepatectomy.A human hepatoma cell line HepG2 was cultured in vitro,and PGC-1αwas knocked down by RNA interference.The expression of PGC-1αwas tested by qPCR and Western blotting,the expression of SIRT3 was tested by Western blotting.Results SIRT3 expression in the HCC tissues was significantly lower than the para-tumorous tissues,the difference was statistically significant(P<0.05).Knockdown of PGC-1αprotein significantly decreased the expression of SIRT3.Conclusion SIRT3 plays an important role of inhibiting tumor growth in HCC.The down-regulation of PGC-1αin hepatoma cell line HepG2 can reduce the expression level of SIRT3 protein and affect its anti-tumor function.