乙酰辅酶A羧化酶2通过调控细胞周期促进肝癌细胞增殖

Promotion of the proliferation of hepatocellular carcinoma cells by acetyl-CoA carboxylase 2 through cell cycle regulation

摘要

目的 研究乙酰辅酶A羧化酶2（acetyl-co carboxylase 2，ACC2）对肝癌细胞增殖、迁移能力的影响以及其潜在的作用机制。 方法 通过TCGA、GEO、CPTAC数据库对ACC2在肝癌（hepatocellular carcinoma，HCC）患者肝脏组织中的表达和预后价值进行分析。采用CRISPR-Cas9系统构建了ACC2敲低肝癌细胞系，观察肝癌细胞增殖、迁移能力以及细胞周期的变化，Western blot实验检测细胞周期相关蛋白的表达。 结果 ACC2在肝癌组织中低表达（P<0.05）且与预后不良相关（P<0.05）。体外细胞功能学实验表明降低ACC2表达显著促进肝癌细胞增殖、迁移能力（P<0.05）。细胞周期流式分析显示敲低ACC2促进肝癌细胞周期G1/S期的转变（P<0.05），细胞周期相关蛋白中CyclinE2和p21的表达降低，而CyclinA2和p-RB的表达升高。 结论 ACC2可以促进肝癌细胞增殖和迁移的能力，对细胞增殖的促进作用是通过加速肝癌细胞周期G1向S期的转化实现的。

Abstract

Objective To investigate the impact of acetyl-CoA carboxylase 2（ACC2） on the proliferation and migration of hepatocellular carcinoma cells（HCCs） as well as the potential mechanism of action. Methods The expression of ACC2 in the liver tissue of patients with HCC and its prognostic significance were analyzed in The Cancer Genome Atlas， Gene Expression Omnibus，and Clinical Proteomic Tumor Analysis Consortium databases. The ACC2-knockdown cell lines of HCCs were established using the CRISPR-Cas9 system；the changes in proliferation，migration，and cell cycle of the HCCs were observed. The expression of cell cycle-related proteins was measured using Western blot assay. Results ACC2 showed low expression in the HCC tissue（P<0.05） and was associated with unfavorable prognoses（P<0.05）. In vitro cell functional experiments revealed that the decrease in ACC2 expression significantly enhanced the proliferation and migration of the HCCs（P<0.05）. Flow cytometric analysis of cell cycles proved that ACC2 knockdown promoted the G1/S phase transition（P<0.05），with decreased expression of CyclinE2 and p21 and increased expression of CyclinA2 and p-RB among the cell cycle-related proteins. Conclusion ACC2 promotes the proliferation and migration of HCCs，which is achieved by accelerating the G1-to-S phase transition of the HCCs.

关键词

肝癌 / 细胞增殖 / 细胞周期 / 乙酰辅酶A羧化酶2

Key words

hepatocellular carcinoma / cell proliferation / cell cycle / acetyl-COA carboxylase 2

基金资助

国家自然科学基金资助项目(82072286)

国家自然科学基金资助项目(82272975)

重庆市教委科学技术研究计划资助项目(KJZD-M202000401)