长链非编码RNA NRAV在肝癌组织和细胞中的表达及其对癌细胞糖酵解的影响  

The expression of long non-coding RNA NRAV in HCC tissues and cells and its effect on cancer cell glycolysis

作　　者：王田园 江伟 肖雪莲 郭成[3] 涂康生[3] WANG Tianyuan;JIANG Wei;XIAO Xuelian;GUO Cheng;TU Kangsheng(Department of Clinical Laboratory,Huazhong University of Science and Technology Union Shenzhen Hospital,Guangdong Shenzhen 518000,China;School of Nursing,Shaoyang University,Hunan Shaoyang 422000,China;Department of Hepatobiliary Surgery,the First Affiliated Hospital of Xi'an Jiaotong University,Shaanxi Xi'an 710061,China)

机构地区：[1]华中科技大学协和深圳医院检验科,广东深圳518000 [2]邵阳学院护理学院,湖南邵阳422000 [3]西安交通大学第一附属医院肝胆外科,陕西西安710061

出　　处：《现代肿瘤医学》2023年第22期4141-4146,共6页Journal of Modern Oncology

基　　金：陕西省重点研发计划项目(编号:2021SF-225);广东省深圳市南山区科技计划项目(编号:NS2021026);华中科技大学协和深圳医院院级课题(编号:YN2021021)。

摘　　要：目的:探究长链非编码RNA抗病毒反应的负调节剂(negative regulator of antiviral response,NRAV)在肝癌组织和细胞中的表达情况及其对肝癌细胞糖酵解和6磷酸果糖2激酶/果糖-2,6-二磷酸酶3(6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3,PFKFB3)表达的影响。方法:RT-qPCR检测NRAV和PFKFB3 mRNA表达。通过转染shRNA或过表达质粒下调或上调肝癌细胞中NRAV表达,通过检测葡萄糖摄取、乳酸生成和ATP水平评估肝癌细胞糖酵解能力。通过Western blotting检测PFKFB3蛋白水平。结果:NRAV在肝癌组织中表达显著高于癌旁组织。NRAV在肝癌细胞系(Hep3B、PLC/PRF/5、HCCLM3、SK-Hep-1和Huh7)中的表达均显著高于正常肝细胞系(MIHA)。干扰NRAV显著减少肝癌细胞葡萄糖摄取、乳酸生成和ATP水平,而过表达NRAV显著增强肝癌细胞糖酵解。肝癌组织中NRAV与PFKFB3 mRNA表达显著正相关,敲低NRAV显著降低肝癌细胞中PFKFB3表达,而过表达NRAV显著上调PFKFB3表达。结论:NRAV在肝癌组织和细胞中表达上调,其促进肝癌细胞糖酵解并增强PFKFB3表达,提示NRAV是一个潜在的抗肝癌治疗新靶标。Objective:To explore the expression of long non-coding RNA negative regulator of antiviral response(NRAV) in hepatocellular carcinoma(HCC) tissues and cells and its effect on glycolysis and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3) expression in HCC cells.Methods:RT-qPCR was carried out to detect NRAV and PFKFB3 mRNA expression.The expression of NRAV was downregulated or upregulated by transfecting shRNA or overexpression plasmid in HCC cells.The glycolysis of HCC cells was evaluated by detecting glucose uptake,lactate production and ATP levels.The expression of PFKFB3 protein level was detected by Western blotting.Results:NRAV expression in HCC tissues was significantly higher than that in tumor-adjacent tissues.The levels of NRAV in HCC cell lines(Hep3B,PLC/PRF/5,HCCLM3,SK-Hep-1 and Huh7) were significantly higher than that normal hepatic cell line(MIHA).NRAV knockdown significantly reduced the glucose uptake,lactate production,and ATP levels of HCC cells.While NRAV overexpression markedly enhanced the glycolysis of HCC cells.NRAV was significantly positively correlated with PFKFB3 mRNA expression in HCC tissues.The knockdown of NRAV significantly decreased the expression of PFKFB3 in HCC cells,while NRAV overexpression prominently increased PFKFB3 expression.Conclusion:NRAV expression is up-regulated in HCC tissues and cell lines.NRAV promotes the glycolysis of HCC cells and enhances PFKFB3 expression,suggesting that NRAV is a potential new target for anti-HCC therapy.

关 键 词：肝癌 抗病毒反应的负调节剂(NRAV) 糖酵解 治疗靶标 

分 类 号：R735.7[医药卫生—肿瘤]