Copper in hepatocellular carcinoma： A double-edged sword with therapeutic potentials

Yu, Qingsheng; Lv, Guishuai; Xing, Fing; Wang, Xiang; Ma, Yue; Feng, Qiyu; Yang, Wen; Wang, Hongyang

doi:10.1016/j.canlet.2023.216348

Cited by 11 publications

(5 citation statements)

References 147 publications

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“…The results of functional enrichment showed that cuproptosis-related genes were jointly involved in the processes of copper homeostasis, glyoxylate metabolism, glycine degradation, cellular response to chemical stress, and blood coagulation. Wu et al reported that an imbalance of copper homeostasis could lead to detrimental outcomes to the liver even the occurrence of liver cancer . Ye et al uncovered that oxalate and glycolate remarkably upregulated in recurrent HCC patients after surgery .…”

Section: Discussionmentioning

confidence: 99%

“…Wu et al reported that an imbalance of copper homeostasis could lead to detrimental outcomes to the liver even the occurrence of liver cancer. 37 Ye et al uncovered that oxalate and glycolate remarkably upregulated in recurrent HCC patients after surgery. 38 Mukha et al found the crucial role of glycine cleavage system in maintaining mitochondrial protein lipoylation to support HCC growth.…”

Section: Discussionmentioning

confidence: 99%

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Construction of a Novel Cuproptosis-Related ceRNA Network-SNHG3/miR-1306-5p/PDHA1 and Identification of SNHG3 as a Prognostic Biomarker in Hepatocellular Carcinoma

Pan,

Zhang,

et al. 2023

ACS Omega

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The crucial role of competitive endogenous RNA (ceRNA) in the malignant biological behavior of tumors has been certificated. Nevertheless, the detailed function and molecular mechanism of ceRNA associated with cuproptosis in hepatocellular carcinoma (HCC) remains dismal. In this study, we first constructed a protein–protein interaction network and identified the module with the highest degree of aggregation degree. DLAT and PDHA1 were screened out of the module after differential expression and survival analysis. Next, we reverse-predicted the upstream miRNA and lncRNA from mRNA (DLAT, PDHA1) and successfully established the ceRNA network-SNHG3/miR-1306-5p/PDHA1. SNHG3 was identified to be an independent prognostic biomarker based on the outcome of univariate and multivariate Cox analyses. Subsequently, we implemented methylation, immune infiltration, and drug sensitivity analysis to investigate the potential biological functions of SNHG3 in HCC. In addition, SNHG3 expression was upregulated in liver cancer cell lines. In vitro functional assay revealed that SNHG3 knockdown significantly attenuated proliferation, migration, and invasion of liver cancer cells. In summary, SNHG3 exhibited oncogenic characterization via sponging miR-1306-5p to regulate PDHA1, which might function as a promising prognostic indicator and a potential therapeutic target for HCC and shed new light on the molecular mechanism of HCC progression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Construction of a Novel Cuproptosis-Related ceRNA Network-SNHG3/miR-1306-5p/PDHA1 and Identification of SNHG3 as a Prognostic Biomarker in Hepatocellular Carcinoma

Pan,

Zhang,

et al. 2023

ACS Omega

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“…Elevated copper levels are critical not only for the development of CRC but also for its metastasis, particularly to the liver, which is the most common site of distant CRC metastasis and a storage organ for copper. 14 Recent studies have shown that copper levels in CRC liver metastases are significantly higher than those in normal liver tissues. 112 Additionally, copper and copper‐binding proteins are vital for epithelial‐mesenchymal transition (EMT) and angiogenesis in CRC metastasis.…”

Section: Role Of Copper and Cuproptosis In Crcmentioning

confidence: 99%

“…Serum copper concentrations in healthy adults typically range from 70 mg/dL to 110 mg/dL. 13 To maintain cellular health and avoid toxicity, the concentration of free copper in the cytoplasm varies from 10 −15 M to 10 −21 M. 14 The intestinal tract is the centre of copper absorption and regulation, primarily mediated by Copper Transport Protein 1 (CTR1, Solute Carrier Family 31 member 1, SLC31A1, encoded by slc31a1) localised in the apical side of epithelial cells. After absorption through the gastrointestinal tract, copper ions are secreted into the bloodstream and bind to soluble chaperones such as ceruloplasmin, transcuprein, histidines, albumin and macroglobulins.…”

Section: Introductionmentioning

confidence: 99%

Copper in colorectal cancer: From copper‐related mechanisms to clinical cancer therapies

Wang,

Pei,

Yang

et al. 2024

Clinical & Translational Med

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Copper, a trace element and vital cofactor, plays a crucial role in the maintenance of biological functions. Recent evidence has established significant correlations between copper levels, cancer development and metastasis. The strong redox‐active properties of copper offer both benefits and disadvantages to cancer cells. The intestinal tract, which is primarily responsible for copper uptake and regulation, may suffer from an imbalance in copper homeostasis. Colorectal cancer (CRC) is the most prevalent primary cancer of the intestinal tract and is an aggressive malignant disease with limited therapeutic options. Current research is primarily focused on the relationship between copper and CRC. Innovative concepts, such as cuproplasia and cuproptosis, are being explored to understand copper‐related cellular proliferation and death. Cuproplasia is the regulation of cell proliferation that is mediated by both enzymatic and nonenzymatic copper‐modulated activities. Whereas, cuproptosis refers to cell death induced by excess copper via promoting the abnormal oligomerisation of lipoylated proteins within the tricarboxylic acid cycle, as well as by diminishing the levels of iron‐sulphur cluster proteins. A comprehensive understanding of copper‐related cellular proliferation and death mechanisms offers new avenues for CRC treatment. In this review, we summarise the evolving molecular mechanisms, ranging from abnormal intracellular copper concentrations to the copper‐related proteins that are being discovered, and discuss the role of copper in the pathogenesis, progression and potential therapies for CRC. Understanding the relationship between copper and CRC will help provide a comprehensive theoretical foundation for innovative treatment strategies in CRC management.

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“…Hanson et al presented a systematic review of the growth, challenges, and future perspectives of paraptosis research in cancer treatment, which will help to develop potential therapy and combat chemoresistance in various cancer. Cuproptosis, a newly defined regulation form of cell death, is mediated by the accumulation of copper ions in cells and related to protein lipoacylation ( Hadian and Stockwell, 2023 ; Wu et al, 2023 ). Ma et al found that an eight-lncRNA signature (TSPOAP1-AS1, AC107464.3, AC006449.7, LINC00324, COLCA1, HAGLR, MIR4435-2HG, and NKILA) linked to cuproptosis was identified, which may improve lung adenocarcinoma management strategies.…”

mentioning

confidence: 99%

Editorial: Different cell death modes in cancer treatment

Bai,

Dou,

Saleh

et al. 2023

Front. Pharmacol.

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Copper in hepatocellular carcinoma： A double-edged sword with therapeutic potentials

Cited by 11 publications

References 147 publications

Construction of a Novel Cuproptosis-Related ceRNA Network-SNHG3/miR-1306-5p/PDHA1 and Identification of SNHG3 as a Prognostic Biomarker in Hepatocellular Carcinoma

Construction of a Novel Cuproptosis-Related ceRNA Network-SNHG3/miR-1306-5p/PDHA1 and Identification of SNHG3 as a Prognostic Biomarker in Hepatocellular Carcinoma

Copper in colorectal cancer: From copper‐related mechanisms to clinical cancer therapies

Editorial: Different cell death modes in cancer treatment

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