SIRT4在肝癌中的表达及其对肝癌细胞增殖和侵袭迁移的影响

Expression of SIRT4 in HCC and its effect on proliferation, invasion and migration of HCC cells

目的检测原发性肝癌组织及配对癌旁组织中沉默调节蛋白SIRT4的表达,及其与原发性肝癌临床病理因素的关系;探索SIRT4对肝癌细胞增殖、侵袭、迁移和对上皮间质转化能力的影响。方法qRT-PCR检测SIRT4在肝癌组织和癌旁组织中的表达;卡方检验(χ^2)分析SIRT4表达与肝癌临床病理因素之间的关系;利用慢病毒转染技术构建SIRT4表达上调的SMMC-7721肝癌细胞系;MTT和Transwell小室观察SIRT4表达对SMMC-7721细胞增殖、迁移和侵袭能力的影响;Western blot检测SIRT4对细胞转化生长因子-β(transforming growth factor-β,TGF-β)和上皮间质转化相关蛋白表达的调控作用。结果原发性肝癌组织中的SIRT4表达明显低于癌旁组织(P<0.01),SIRT4低表达与肝癌的临床病理因素密切相关;过表达SIRT4抑制SMMC-7721肝癌细胞增殖、迁移、侵袭和上皮间质转化能力。结论SIRT4在原发性肝癌中可能扮演抑癌基因角色,并可成为肝癌的潜在生物标记物和治疗靶点。

Objective To investigate the expression of silencing regulator protein SIRT4 in hepatocellular carcinoma(HCC) and para-cancerous tissue and reveal its relationship with clinical pathologic factors of HCC. To reveal the effects of SIRT4 on proliferation, invasion, migration and epithelial mesenchymal transformation of HCC cells. Methods Real-time quantitative qRT-PCR was used to detect the difference of the expression of SIRT4 in HCC tissues and adjacent tissues. The correlation between SIRT4 expression level and the clinicopathologic factors of HCC was analyzed by chi square test. Lentiviral transfection was used to build SIRT4 overexpression SMMC-7721 cell lines. MTT assay and Transwell assay were used to detect the effect of SIRT4 on proliferation, migration and invasion of HCC cells. Western-blot assay was used to detect the expression of transforming growth factor-β(TGF-β) and epithelial-mesenchymal transition proteins in two groups. Results The expression of SIRT4 in HCC was significantly lower than that in para-cancer tissue(P<0.01). The expression level of SIRT4 in SMMC-7721-SIRT4 group was significantly higher than that in SMMC-7721-NC group(P<0.01). Compared with SMMC-7721-NC group, SMMC-7721-SIRT4 cells showed significantly lower ability in proliferation, migration, invasion and EMT. Conclusion SIRT4 is lower in HCC tissue and its down-regulated expression is associated with adverse clinicopathologic factors. Overexpression of SIRT4 can significantly inhibit the malignant biological behavior of HCC cells. SIRT4 may serve as a cancer suppressor gene and can be a potential biomarker and therapeutic target for HCC.