ArticleOncology letters2023
Oncogenic role of copper‑induced cell death‑associated protein DLD in human cancer: A pan‑cancer analysis and experimental verification.
Article in Oncology letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 22 citations in OpenAlex.
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- Regulation of mitochondrial iron homeostasis in tumor cells.Molecular medicine (Cambridge, Mass.) · 2026Review
- Cisplatin resistance in ovarian cancer: exploration and insights from metal ion homeostasis imbalance.Frontiers in cell and developmental biology · 2026Review
- Advancing the frontiers of ovarian cancer therapy: a comprehensive synthesis of emerging cell death paradigms.Oncology reviews · 2026Review
- Copper Homeostasis and Cuproptosis As Potential Intervention Strategy in Atherosclerosis.Journal of cardiovascular translational research · 2025Review
- Cuproptosis: molecular mechanisms, cancer prognosis, and therapeutic applications.Journal of translational medicine · 2025Review
- To Explore the Mechanism of Cuproptosis in Psoriasis Based on Bioinformatics and in vivo Experiments.Journal of inflammation research · 2025Article
- Immunomodulatory Effects of SPHK1 and Its Interaction with TFAP2A in Yellow Drum (International journal of molecular sciences · 2024Article
- Pharmacoproteomics reveals energy metabolism pathways as therapeutic targets of ivermectin in ovarian cancer toward 3P medical approaches.The EPMA journal · 2024Article
- Quercetin Attenuates Acute Kidney Injury Caused by Cisplatin by Inhibiting Ferroptosis and Cuproptosis.Cell biochemistry and biophysics · 2024Article
- A cuproptosis-related prognostic signature for guiding clinical diagnosis and treatment in uveal melanoma patients.Heliyon · 2024Article
- Cuproptosis in lung cancer: mechanisms and therapeutic potential.Molecular and cellular biochemistry · 2024Review
- Cuproptosis: Unraveling the Mechanisms of Copper-Induced Cell Death and Its Implication in Cancer Therapy.Cancers · 2024Review
- Roles of Dihydrolipoamide Dehydrogenase in Health and Disease.Antioxidants & redox signaling · 2023Review
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2 authors at 1 institution in 1 country.
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Abstract
Copper ions can bind directly to lipoylated components of the tricarboxylic acid (TCA) cycle, triggering the aggregation of mitochondrial lipoylated proteins and the destabilization of Fe-S cluster proteins, resulting in copper-dependent cell death. Dihydrolipoamide dehydrogenase (DLD) is a key protein of the TCA cycle and constitutes the E3 component of the α-ketoglutarate dehydrogenase complex, which is deeply interconnected with the mitochondrial electron transfer chain in the TCA cycle. Tumor cells demonstrate dependency on glutaminolysis fuelling to carry out the TCA cycle and essential biosynthetic processes supporting tumor growth. Therefore, DLD plays an important role in the tumor biological process. However, to the best of our knowledge, no pan-cancer analysis is currently available for DLD. Therefore, the present study first explored the DLD expression profile in 33 tumors in publicly available datasets, including TIMER2, GEPIA2, UALCAN, cBioPortal and STRING. TIMER2, GEPIA2 and UALCAN were used for exploring gene expression; survival prognosis was detected by GEPIA2; genetic alteration was analysed by cBioPortal; immune infiltration data was obtained from TIMER2; interacting proteins of DLD were detected by STRING. DLD was found to be highly expressed in colon, liver, lung, stomach, renal, corpus uteri endometrial and ovarian cancers compared with normal tissues, and its high expression was associated with poorer prognosis in ovarian cancer. To the best of our knowledge, the present study provided the first comprehensive pan-cancer analysis of the oncogenic role of DLD across different tumors types. As the expression of DLD in ovarian cancer was high, and high expression is associated with poor prognosis, experimental verification of DLD in ovarian cancer was conducted. In the present study, DLD expression was found to be high in the ovarian cancer OC3 cell line, compared with the normal ovarian epithelial IOSE80 cell line by reverse transcription-quantitative PCR analysis. After knockdown of DLD expression, it was found that DLD regulated metabolic pathways by suppressing the intracellular NAD
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