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NAMPT基因对肾癌细胞增殖和凋亡的影响及其机制研究
引用本文:王艳辉,柳雅慧,任丽. NAMPT基因对肾癌细胞增殖和凋亡的影响及其机制研究[J]. 天津医科大学学报, 2021, 0(4): 343-348,378
作者姓名:王艳辉  柳雅慧  任丽
作者单位:(天津医科大学肿瘤医院检验科,国家肿瘤临床医学研究中心,天津市“肿瘤防治”重点实验室,天津市恶性肿瘤临床医学研究中心,天津300060)
摘    要:目的:探讨烟酰胺磷酸核糖转移酶(NAMPT)在肾癌中的表达情况及对肾癌细胞增殖和凋亡的影响.方法:通过TCGA在线数据库ualcan分析NAMPT在肾癌组织和正常肾组织中的表达,通过Kaplan-Meier plotter数据库分析NAMPT对肾癌预后的影响.qPCR检测NAMPT基因在肾癌细胞769P、A704、78...

关 键 词:肾癌  NAMPT  增殖  细胞凋亡

The effect of NAMPT on the proliferation and apoptosis of renal cell carcinoma and its mechanism
WANG Yan-hui,LIU Ya-hui,REN Li. The effect of NAMPT on the proliferation and apoptosis of renal cell carcinoma and its mechanism[J]. Journal of Tianjin Medical University, 2021, 0(4): 343-348,378
Authors:WANG Yan-hui  LIU Ya-hui  REN Li
Affiliation:(Department of Laboratory,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Tianjin Key Laboratory of Cancer Prevention and Therapy,Tianjin Clinical Research Center for Cancer,Tianjin 300060,China)
Abstract:Objective: To investigate the expression of nicotinamide phosphoribosyl transferase(NAMPT) in renal cell carcinoma and its effect on the proliferation and apoptosis of renal cell carcinoma. Methods: The TCGA online database ualcan was used to analyze the expression of NAMPT in renal cancer tissues and normal renal tissues,the Kaplan-Meier plotter database was used to analyze the influence of NAMPT on the prognosis of renal cancer. qPCR was used to detect the expression of NAMPT gene in renal cancer cell 769P,A704,786-O and normalized renal tubular epithelial cells HK 2. 786-O cell was transfected with NAMPT specific shRNA(shNAMPT group) and control sequence(scramble group) respectively,and treated with NAMPT inhibitor FK866 and control reagent DMSO. CCK-8 assay,cell colony formation assay and flow cytometry were respectively used to detect cell proliferation,the cloning ability and apoptosis of 786-O cell. NAD+/NADH detection kit was used to detect the content of nicotinamide adenine dinucleotide(NAD+) in cells. Western blotting assay was used to detect the expression of NAMPT and the effect of interfering with NAMPT on phosphatidylinositol 3 kinase/protein kinase B (PI3K / Akt) pathway. Results: Bioinformatics analysis showed that the expression of NAMPT in renal cell carcinoma was higher than that in normal renal tissues(P<0.05). The overall survival rate was significantly reduced in patients with high expression of NAMPT group than those in patients with low expression of NAMPT group(P<0.01);the expression of NAMPT were higher in 769P,A704,786-O than those in renal tubular epithelial cells HK2(t=6.680,P=0.0026,t=14.12,P=0.001,t=13.43,P=0.002).Cytological experiment results showed that compared with DMSO group,in FK866 group,786-O cell proliferation and clone formation ability was significantly inhibited(t=2.625,P<0.05,t=5.687,P<0.01),and the proportion of apoptotic cells was increased(t=6.325,P<0.01),the production of NAD+ was significantly decreased (t=17.62,P<0.001).Compared with scramble group,in shNAMPT group,786-O cell proliferation and clone formation ability was significantly inhibited(t=3.959,P<0.05,t=8.684,P<0.05),and the proportion of apoptotic cells was increased(t=14.05,P<0.01),the production of NAD+ was significantly decreased(t=10.93,P<0.001),and the expression of key proteins p-PI3K and p-Akt of the Akt pathway were significantly down-regulated(t=7.721,P<0.01,t=14.78,P<0.001). Conclusion: NAMPT is highly expressed in renal cell carcinoma and is related to the poor prognosis of patients. Interfering with the expression of NAMPT can reduce the production of NAD+ and inhibit the activation of PI3K/Akt pathway,thereby reducing the proliferation and promoting apoptosis of renal cancer cells.
Keywords:renal cancer  NAMPT  proliferation  apoptosis
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