Clinical Research Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Allergy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Aging (Albany NY). 2023 Sep 13;15(17):9193-9216. doi: 10.18632/aging.205028.
Aldosterone-producing adenoma (APA), characterized by unilaterally excessive aldosterone production, is a common cause of primary aldosteronism. Ferroptosis, a recently raised iron-dependent mode of programmed cell death, has been involved in the development and therapy of various diseases. This study obtained datasets of the mRNA and lncRNA expression profiles for APA and adjacent adrenal gland (AAG) from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and lncRNAs (DE lncRNAs) associated with ferroptosis were identified. Enrichment analyses indicated 89 ferroptosis-related DEGs were primarily enriched in ROS related processes and ferroptosis. Two physical cores, and one combined core were identified in the protein-protein interaction (PPI). DEGs and clinical traits were used in conjunction to screen eight hub genes from two hub modules and 89 DEGs. A competitive endogenous RNA (ceRNA) network was constructed via co-express analysis. Thereafter, molecular docking was used to identify potential targets. Two active compounds, QL-X-138 and MK-1775, bound to AURKA and DUOX1, respectively, with the lowest binding energies. Molecular dynamics simulation verified the stability of the two complexes. In summary, our studies identified eight hub genes and a novel ceRNA regulatory network associated with ferroptosis, wherein QL-X-138 and MK-1775 were considered to be potential drugs for treating APA.
醛固酮瘤 (APA) 以单侧过量醛固酮产生为特征,是原发性醛固酮增多症的常见病因。铁死亡是一种新提出的、依赖铁的程序性细胞死亡方式,与多种疾病的发生和治疗有关。本研究从基因表达综合数据库 (GEO) 中获得了 APA 和相邻肾上腺 (AAG) 的 mRNA 和 lncRNA 表达谱数据集。鉴定了与铁死亡相关的差异表达基因 (DEGs) 和 lncRNA (DE lncRNAs)。富集分析表明,89 个与铁死亡相关的 DEGs 主要富集在 ROS 相关过程和铁死亡中。通过蛋白质-蛋白质相互作用 (PPI) 鉴定出两个物理核心和一个组合核心。DEGs 和临床特征联合用于从两个枢纽模块和 89 个 DEGs 中筛选出 8 个枢纽基因。通过共表达分析构建竞争性内源 RNA (ceRNA) 网络。然后,通过分子对接鉴定潜在的靶标。两种活性化合物 QL-X-138 和 MK-1775 分别与 AURKA 和 DUOX1 结合,结合能最低。分子动力学模拟验证了两个复合物的稳定性。总之,我们的研究鉴定了 8 个与铁死亡相关的枢纽基因和一个新的 ceRNA 调控网络,其中 QL-X-138 和 MK-1775 被认为是治疗 APA 的潜在药物。