【摘 要】
：
乙酰辅酶A羧化酶1(acetyl-CoA carboxylase1,ACC1)是脂肪酸合成途径的限速酶.ACC1与多种代谢性疾病和癌症密切相关.然而,ACC1在肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)中的作用及机制却未见报道.本研究以肾透明细胞癌786-O和Caki-1细胞为对象,探讨ACC1异常表达对肾透明细胞癌增殖的影响及其作用机制.首先通过红油-O-染色发现,相比HK2(human kidney-2)细胞,786-O和Caki-1细胞中的脂肪含量明显
【机 构】
：
昆明医科大学基础医学院生物化学与分子生物学系,昆明650500;昆明医科大学第一附属医院器官移植科,昆明650032;昆明医科大学第一附属医院病理科,昆明650032
论文部分内容阅读
乙酰辅酶A羧化酶1(acetyl-CoA carboxylase1,ACC1)是脂肪酸合成途径的限速酶.ACC1与多种代谢性疾病和癌症密切相关.然而,ACC1在肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)中的作用及机制却未见报道.本研究以肾透明细胞癌786-O和Caki-1细胞为对象,探讨ACC1异常表达对肾透明细胞癌增殖的影响及其作用机制.首先通过红油-O-染色发现,相比HK2(human kidney-2)细胞,786-O和Caki-1细胞中的脂肪含量明显增加.检索TCGA数据库分析发现,ACC1的蛋白质水平在肾透明细胞癌组织中的表达显著高于正常肾组织(P＜0.001).由分期分级分析发现,临床TNM各期的ACC1蛋白表达均显著高于正常组织.且ACC1表达水平越高,病理分级越高.而ACC1的mRNA水平高表达与肾透明细胞癌病人的不良预后呈正相关.West-ern印迹结果显示,与对照组HK2细胞相比,在786-O和Caki-1细胞中,ACC1的表达明显增加.通过慢病毒载体构建ACC1敲低的稳转细胞株,由红油-O-染色结果显示,ACC1敲低可显著降低786-O和Caki-1细胞的脂肪含量.CCK-8和平板克隆结果显示,ACC1低表达可显著降低786-O和Ca-ki-1细胞的增殖和克隆形成能力.流式细胞周期结果显示,ACC1敲低可使细胞周期G0/G1期阻滞,并且抑制细胞周期蛋白D1(cyclinD1)和CDK4表达.以上结果表明,ACC1在肾透明细胞癌中异常高表达,并通过上调细胞周期蛋白D1和CDK4表达调控细胞周期进程,促进肿瘤增殖,提示不良预后,ACC1有望成为ccRCC干预治疗的潜在新靶点.
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