研究动态
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已证实Cuproptosis相关基因PDHB被鉴定为与透明细胞肾细胞癌发展呈负相关的生物标记物。

Cuproptosis related gene PDHB is identified as a biomarker inversely associated with the progression of clear cell renal cell carcinoma.

发表日期:2023 Aug 28
作者: Hu Wang, Zhan Yang, Xingyu He, Fengran Guo, Hao Sun, Sen Xu, Chao Xu, Zhu Wang, Hongzhuang Wen, Zhihai Teng, Yaxuan Wang, Zhenwei Han
来源: GENES & DEVELOPMENT

摘要:

氧化铜引发的线粒体呼吸障碍介导的新发现的一种程序性细胞死亡,被称为cupoptosis。丙酮酸脱氢酶E1亚单位β(PDHB)是cupoptosis基因之一,是核编码的丙酮酸脱氢酶,催化丙酮转化为乙酰辅酶A。然而,PDHB在透明细胞肾细胞癌(ccRCC)中的作用机制尚不清楚。我们使用TCGA和GEO的数据评估了PDHB在正常和肿瘤组织中的表达水平。我们进一步分析了PDHB与体细胞突变和免疫浸润的关系。最后,我们初步探讨了PDHB对ccRCC的影响。PDHB的表达水平在肿瘤组织中低于正常组织。与此同时,PDHB的表达水平在高级别肿瘤中也低于低级别肿瘤。PDHB与ccRCC的预后呈正相关。此外,PDHB可能与VHL、PBRM1和KDM5C突变的风险降低有关。在786-O细胞中,氯化铜可促进cupoptosis基因(DLAT、PDHB和FDX1)的表达,抑制细胞生长。最后但并非最不重要的是,我们发现PDHB可以抑制ccRCC细胞的增殖和迁移。我们的结果表明PDHB可以抑制ccRCC细胞的增殖、迁移和侵袭,可能是ccRCC的预后预测因子。针对该分子靶向治疗可能为晚期ccRCC患者提供新的治疗策略。© 2023 BioMed Central Ltd.,施普林格自然出版集团的一部分。
Cuproptosis is a newly discovered programmed cell death dependent on mitochondrial respiratory disorder induced by copper overload. Pyruvate dehydrogenase E1 subunit beta (PDHB) is one of the cuproptosis genesand is a nuclear-encoded pyruvate dehydrogenase, which catalyzes the conversion of pyruvate to acetyl coenzyme A. However, the mechanism of PDHB in clear cell renal cell carcinoma (ccRCC) remains unclear.We used data from TCGA and GEO to assess the expression of PDHB in normal and tumor tissues. We further analyzed the relationship between PDHB and somatic mutations and immune infiltration. Finally, we preliminarily explored the impact of PDHB on ccRCC.The expression level of PDHB was lower in tumor tissue compared with normal tissue. Meanwhile, the expression level of PDHB was also lower in high-grade tumors than low-grade tumors. PDHB is positively correlated with prognosis in ccRCC. Furthermore, PDHB may be associated with decreased risk of VHL, PBRM1 and KDM5C mutations. In 786-O cells, copper chloride could promote the expression of cuproptosis genes (DLAT, PDHB and FDX1) and inhibit cell growth. Last but not least, we found that PDHB could inhibit the proliferation and migration of ccRCC cells.Our results demonstrated that PDHB could inhibit the proliferation, migration and invasion in ccRCC cells, which might be a prognostic predictor of ccRCC. Targeting this molecular might provide a new therapeutic strategy for patients with advanced ccRCC.© 2023. BioMed Central Ltd., part of Springer Nature.