Comprehensive Bioinformatics Analysis Reveals the Role of Shared Cuproptosis- and Ferroptosis-Related DEG DLD in Abdominal Aortic Aneurysm

Xingwei Hu, Lu Hu, Xiaoyun Si, Qian Feng, Yi Ma, Zhijiang Liu, Xiang He, Bei Shi
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Abstract

Ferroptosis plays a crucial role in the progression of abdominal aortic aneurysm (AAA). Cuproptosis, as a new mode of death, has some similarities with ferroptosis. The primary objective of this study was to develop the role of shared cuproptosis-related differentially expressed genes (CRDEGs) and ferroptosis-related differentially expressed genes (FRDEGs) in AAA. RNA sequencing and bioinformatic analyses of human AAA tissue were used to identify dihydrolipoamide dehydrogenase (DLD), which is involved in cuproptosis and ferroptosis. qRT-PCR and IHC assays further confirmed that the DLD level was substantially higher in the AAA group than in the control group. Finally, experimental verification was conducted to identify that DLD could promote the necrosis, apoptosis and mitophagy of SMCs. In summary, our research identified DLD, linked to cuproptosis and ferroptosis, as differentially expressed in AAA across human and murine samples. DLD's role in regulating SMC necrosis, apoptosis and mitophagy positions it as a potential AAA biomarker and therapeutic target, warranting further investigation for clinical applications.

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综合生物信息学分析揭示了共同嗜铜和嗜铁相关的DEG DLD在腹主动脉瘤中的作用
上睑下垂在腹主动脉瘤(AAA)的发展中起着至关重要的作用。铜下垂作为一种新的死亡方式,与铁下垂有一些相似之处。本研究的主要目的是研究共同铜沉相关差异表达基因(CRDEGs)和铁沉相关差异表达基因(FRDEGs)在AAA中的作用,利用RNA测序和生物信息学分析方法鉴定了参与铜沉和铁沉的二氢脂酰胺脱氢酶(DLD)。qRT-PCR和免疫组化检测进一步证实,AAA组DLD水平明显高于对照组。最后通过实验验证,DLD可促进SMCs的坏死、凋亡和有丝分裂。总之,我们的研究确定了DLD,与铜下垂和铁下垂有关,在人类和小鼠样本的AAA中差异表达。DLD在调节SMC坏死、凋亡和线粒体自噬中的作用使其成为潜在的AAA生物标志物和治疗靶点,值得进一步研究其临床应用。
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期刊介绍: The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.
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