DHODH对透明细胞肾细胞癌促癌作用的生物信息学分析及实验验证。
Bioinformatics analysis and experimental verification of the cancer-promoting effect of DHODH in clear cell renal cell carcinoma.
发表日期:2024 May 25
作者:
Songsong Wang, Yan Li, Yilong Lin, Junting Li, Lang Guo, Haoyu Wang, Xinyuan Lin, Ziming Liu, Bingqi Zhang, Zhengming Liao, Zhongmin Zhang
来源:
Immunity & Ageing
摘要:
透明细胞肾细胞癌(ccRCC)是泌尿系统的恶性肿瘤。为了探索 DHODH 在 ccRCC 中的潜在机制,我们使用公共数据库分析了其分子特征。 TCGA泛癌数据集用于分析不同癌症类型中DHODH的表达,TCGA ccRCC数据集用于评估DHODH的差异表达、预后相关性、免疫浸润、单基因和功能富集。利用 GSCALite 和 CellMiner 数据库探索药物并与 DHODH 进行分子对接分析。使用多个数据库构建了 DHODH 的蛋白质-蛋白质相互作用网络和 ceRNA 调控网络。 DHODH 对 ccRCC 的作用在体外得到证实。 DHODH 在 ccRCC 中高表达。免疫浸润分析表明,DHODH可能参与调节Treg等免疫抑制细胞的浸润。值得注意的是,DHODH 通过与 hsa-miR-26b-5p 和 UMPS 等分子形成调控网络来影响 ccRCC 进展,并显着增强 ccRCC 细胞的恶性特征。拉帕替尼、西米塔替尼、伊曲康唑和达沙替尼等多种药物对 DHODH 表达敏感,并与其表现出强烈的分子结合。因此,DHODH 可能促进 ccRCC 进展,是 ccRCC 的候选有效治疗靶点。© 2024。作者。
Clear cell renal cell carcinoma (ccRCC) is a malignant tumor of the urinary system. To explore the potential mechanisms of DHODH in ccRCC, we analyzed its molecular characteristics using public databases. TCGA pan-cancer dataset was used to analyze DHODH expression in different cancer types and TCGA ccRCC dataset was used to assess differential expression, prognosis correlation, immune infiltration, single-gene, and functional enrichment due to DHODH. The GSCALite and CellMiner databases were employed to explore drugs and perform molecular docking analysis with DHODH. Protein-protein interaction networks and ceRNA regulatory networks of DHODH were constructed using multiple databases. The effect of DHODH on ccRCC was confirmed in vitro. DHODH was highly expressed in ccRCC. Immune infiltration analysis revealed that DHODH may be involved in regulating the infiltration of immunosuppressive cells such as Tregs. Notably, DHODH influenced ccRCC progression by forming regulatory networks with molecules, such as hsa-miR-26b-5p and UMPS and significantly enhanced the malignant characteristics of ccRCC cells. Several drugs, such as lapatinib, silmitasertib, itraconazole, and dasatinib, were sensitive to DHODH expression and exhibited strong molecular binding with it. Thus, DHODH may promote ccRCC progression and is a candidate effective therapeutic target for ccRCC.© 2024. The Author(s).