AKAP1在肾透明细胞癌中的表达及对细胞生存的影响

Expression of AKAP1 in renal clear cell carcinoma and its effect on cell survival

目的探讨线粒体外膜蛋白A激酶锚定蛋白1(AKAP1)在肾透明细胞癌(KIRC)中的表达变化及对患者预后和细胞生存的影响。方法利用GEO、TCGA和HPA数据库,分析AKAP1在KIRC组织中的表达变化;利用RT-PCR和Western blot检测8对KIRC组织及其配对癌旁组织中AKAP1 mRNA和蛋白的表达;利用LinkedOmics和GEPIA数据库,分析AKAP1表达与KIRC患者临床病理参数的相关性及对预后的影响;Western blot检测AKAP1过表达后细胞增殖、凋亡相关蛋白表达情况;MTS和流式细胞术检测AKAP1过表达后,KIRC细胞增殖、凋亡情况。结果与癌旁组织比较,AKAP1 mRNA和蛋白表达在KIRC组织中均显著降低,且表达水平与患者病理分级及TNM分期呈负相关(P<0.05);生存分析表明,AKAP1低表达与KIRC患者不良预后相关(P<0.01)。在786-O细胞中过表达AKAP1可显著抑制细胞增殖、促进细胞凋亡(P<0.01)。结论AKAP1在KIRC组织中表达显著降低,可作为KIRC治疗的潜在靶点及预后生物标志物。

Objective To investigate the expression of mitochondrial outer membrane protein 1(AKAP1)in renal clear cell carcinoma(KIRC)and its effect on the prognosis of patients and cell survival.Methods The databases of GEO,TCGA and HPA were used to analyze the change of AKAP1 expression in KIRC tissues.RT-PCR and Western blot were used to detect the expression of AKAP1 mRNA and protein in 8 pairs of KIRC tissues and their adjacent tissues.the LinkedOmics and GEPIA databases were used to analyze the correlation between AKAP1 expression and clinicopathological parameters of KIRC patients and its impact on prognosis.Western blot was conducted to detect the expression of cell proliferation and apoptosis-related proteins after AKAP1 overexpression,MTS and flow cytometry were used to detect the proliferation and apoptosis of AKAP1 cells after AKAP1 overexpression.Results Compared with in paracancerous tissues,the expressions of AKAP1 mRNA and protein in KIRC tissues were significantly reduced,and the expression level was negatively correlated with the patient′s pathological grade and TNM stage(P<0.05).Survival analysis showed that the low expression of AKAP1 was related to the poor prognosis of KIRC patients(P<0.01).Overexpression of AKAP1 in 786-O cells could significantly inhibit cell proliferation and promote apoptosis when compared with 786-O cells without any treatment(P<0.01).Conclusion AKAP1 expression is significantly reduced in KIRC tissues,which can be used as a potential target and prognostic biomarker for KIRC treatment.