丙酮酸脱氢酶E1亚基α1在肾透明细胞癌中的表达及影响

Expression and effect of pyruvate dehydrogenase E1 subunit alpha 1 in clear cell renal cell carcinoma

背景肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)的代谢特征之一是进行有氧糖酵解,探讨糖代谢通路的关键蛋白对ccRCC的影响具有重要临床意义。目的探究丙酮酸脱氢酶E1亚基α1(pyruvate dehydrogenase E1 subunit alpha 1,PDHA1)在ccRCC中的表达及对ccRCC预后的影响,并在体外细胞实验中检测PDHA1对ccRCC细胞系786-O生长、增殖和迁移的影响。方法检索TCGA数据库中的转录组数据,分析PDHA1在ccRCC和癌旁组织中的表达水平,并根据肿瘤分期、分级和淋巴细胞转移情况,比较PDHA1表达差异。应用Kaplan-Meier法分析PDHA1表达与肿瘤预后的关系,通过基因富集分析,预测PDHA1在肿瘤中发挥功能的信号通路。体外细胞实验,Western blot验证786-O转染后PDHA1的蛋白表达情况。通过CCK-8法、克隆形成及划痕实验,检测PDHA1对786-O细胞生长、增殖和迁移的影响。结果TCGA数据库显示,相比于癌旁组织,ccRCC组织的PDHA1 mRNA水平明显下降,PDHA1的mRNA水平也与ccRCC的分期和分级有关(P<0.01)。PDHA1高表达组有较长的无病生存期和总生存期(P<0.01);体外细胞实验结果表明,与空载体相比,高表达PDHA1后,786-O细胞增殖、克隆形成和迁移能力均明显减弱(P<0.01)。结论PDHA1表达与ccRCC患者预后正相关,在抑制肿瘤细胞生长、增殖及迁移中发挥了重要作用。

Background As one of the metabolic characteristics of clear cell renal cell carcinoma(ccRCC)is aerobic glycolysis,it is of great significance to explore the influence of key proteins in glucose metabolism on ccRCC.Objective To study the expression of pyruvate dehydrogenase E1 subunit alpha 1(PDHA1)in ccRCC and its influence on the prognosis of ccRCC,as well as the effect of PDHA1 on the growth,proliferation and migration of ccRCC 786-O cell line in vitro.Methods Using the data from TCGA database,the expression levels of PDHA1 mRNA in ccRCC and adjacent tissues were analyzed.PDHA1 mRNA levels were compared according to the tumor stage,grade and lymph node metastasis.Kaplan-Meier method was used to analyze the relationship between PDHA1 expression and tumor prognosis.The function of PDHA1 in ccRCC was explored by gene enrichment analysis.In vitro,the expression of PDHA1 after transfection was verified by western blot.The effects of PDHA1 on the growth,proliferation and migration of 786-O cells were respectively determined by CCK-8,colony formation and wound healing assay.Results According to TCGA database,PDHA1 mRNA levels significantly decreased in RCCC tissues compared with adjacent tissues.PDHA1 mRNA levels were also related to tumor stage and grade.The high expression group of PDHA1 had longer disease free survival and overall survival.The results in vitro showed that the proliferation,clonogenesis and migration of 786-O cells decreased significantly in PDHA1 overexpression group compared with empty vector group.Conclusion The expression of PDHA1 mRNA is positively correlated with the prognosis of patients with ccRCC,and PDHA1 plays an important role in inhibiting the growth,proliferation and migration of ccRCC cells.