UCP1 modulates immune infiltration level and survival outcome in ovarian cancer patients

Huang, Jinfa; Wang, Guilian; Liao, Kedan; Xie, Ning; Deng, Kaixian

doi:10.1186/s13048-022-00951-z

Cited by 7 publications

(6 citation statements)

References 33 publications

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“…ROS (superoxide) and long-chain fatty acids activate UCP-1, which can be inhibited by purine nucleotides, e.g., ATP [178,179]. There are five isoforms of UCP that have been identified thus far, each with specific functions [180]. An increased expression of UCP-1 has been shown to play a relevant role in immune infiltration by regulating oncogene levels in ovarian cancer [180].…”

Section: Cancer Cell Metabolism Ros and Antioxidant Therapymentioning

confidence: 99%

“…There are five isoforms of UCP that have been identified thus far, each with specific functions [180]. An increased expression of UCP-1 has been shown to play a relevant role in immune infiltration by regulating oncogene levels in ovarian cancer [180]. Based on cancer single-cell sequencing data, tumor functional status analyses suggest that UCP-1 may down regulate invasion, epithelial-mesenchymal transition, metastasis, DNA repair, and angiogenesis.…”

Section: Cancer Cell Metabolism Ros and Antioxidant Therapymentioning

confidence: 99%

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Oxidative Stress and ROS Link Diabetes and Cancer

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2024

JMP

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Type 2 diabetes mellitus (T2DM) accounts for one-sixth of deaths globally, whereas cancer is the second leading cause of death in the U.S. T2DM is a known risk factor for many cancers. Reactive oxygen species (ROS)-altered metabolic and signaling pathways link T2DM to cancer. These reprogrammed metabolic and signaling pathways contribute to diabetic complications, impact the redox balance (oxidative stress), and have differential roles in the early and late stages of cancer. A respiratory chain that is highly reduced (as under hyperglycemic conditions) or if reduced cofactors accumulate, ROS are greatly elevated. ROS may cause mutations in mitochondrial DNA (mtDNA) that result in further ROS elevations. The amplification of ROS results in the activation of PKC, an overarching signaling pathway that activates MAPK with a subsequent regulation in several factors that result in pathophysiological manifestations of T2DM and cancer. An upregulation in PKC leads to a deregulation in NF-kß, which regulates the PKB/P13/Akt pathway and orchestrates the cell survival, growth, proliferation, and glucose metabolism manifested in cancer. It also affects Insulin Receptor Substrate (IRS-1), decreasing insulin-stimulated glucose transport and glucose uptake, disrupting subsequent cell signaling pathways contributing to the development of T2DM. Dyslipidemia is a hallmark of T2DM and cancer. ROS-induced lipid peroxidation leads to systemic inflammation, producing inflammatory prostaglandins, cytokines, and chemokines that result in tumor proliferation, rapid tumor growth, and modulation of immunity. The dual role of ROS in the early and late stages of cancer makes antioxidant therapy precarious and may be responsible for controversial results. A system that delivers an antioxidant directly to mitochondria may be useful in inhibiting the formation of ROS early during the pre-diabetic stage, whereas antioxidant therapy must be halted in later stages to retard metastasis.

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Section: Cancer Cell Metabolism Ros and Antioxidant Therapymentioning

confidence: 99%

Section: Cancer Cell Metabolism Ros and Antioxidant Therapymentioning

confidence: 99%

Oxidative Stress and ROS Link Diabetes and Cancer

Black

2024

JMP

View full text Add to dashboard Cite

show abstract

“…There are five isoforms of UCP that have been identified thus far, each with specific functions [181]. Increased expression of UCP-1 has been shown to play a relevant role in immune infiltration by regulating oncogene levels in ovarian cancer [182]. Based on cancer single cell sequencing data, tumor functional status analyses suggest that UCP-1 may down regulate invasion, epithelial-mesenchymal transition, metastasis, DNA repair, and angiogenesis.…”

Section: Cancer Cell Metabolismmentioning

confidence: 99%

“…Based on cancer single cell sequencing data, tumor functional status analyses suggest that UCP-1 may down regulate invasion, epithelial-mesenchymal transition, metastasis, DNA repair, and angiogenesis. UCP-2 inhibits ROS production that results in reduced ADP yield and reduced insulin secretion [182]. UCP-2 also catalyzes an exchange and transport of intramitochondrial C4 intermediates (e.g., oxaloacetate) that negatively controls oxidation of acetyl-CoA-producing substrates through the Krebs cycle.…”

Section: Cancer Cell Metabolismmentioning

confidence: 99%

Oxidative Stress and ROS Linking Diabetes and Cancer

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2023

Preprint

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Type 2 diabetes mellitus (T2DM) accounts for one-sixth of deaths, globally, whereas cancer is the second leading cause of death in the U.S. T2DM is a known risk factor for many cancers. This review examines the link of Reactive oxygen Species (ROS)-altered metabolic and signaling pathways in T2DM to cancer. These reprogrammed metabolic and signaling pathways are activated that contribute to diabetic complications, impact redox balance (Oxidative Stress), and have differential roles in early and late stages of cancer. If the respiratory chain is highly reduced (as under hyperglycemic conditions) or if reduced cofactors accumulate, ROS are greatly elevated. ROS may cause mutations in mitochondrial DNA (mtDNA) that result in further ROS elevation. Amplification of ROS results in activation of PKC, an overarching signaling pathway that activates MAPK with subsequent regulation of several factors that result in pathophysiological manifestations of T2DM and cancer. Upregulation of PKC leads to deregulation of NF-kß that regulates the PKB/P13/Akt pathway that orchestrates cell survival, growth, proliferation, and glucose metabolism manifested in cancer. It also affects Insulin Receptor Substrate (IRS-1), decreasing insulin stimulated glucose transport and glucose uptake, disrupting subsequent cell signaling pathways contributing to the development of T2DM. Dyslipidemia is a hallmark of T2DM and cancer. ROS-induced lipid peroxidation leads to systemic inflammation, producing inflammatory prostaglandins, cytokines and chemokines that result in tumor proliferation, rapid tumor growth, and modulation of immunity. The dual role of ROS in early and late stages of cancer make antioxidant therapy precarious and may be responsible for controversial results. A system that delivers an antioxidant directly to mitochondria may be useful in inhibiting formation of ROS early during the pre-diabetic stage whereas antioxidant therapy must be halted in later stages to retard metastasis.

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“…In breast cancer, researchers utilizing public datasets combined with comprehensive bioinformatic analysis established an efficient prognostic signature containing 11 ferroptosis-associated genes. Furthermore, various immune-related biological processes were gathered to participate in the model [ 15 , 25 ]. Some researchers also reported prognostic prediction signatures constructed with ferroptosis-related genes (FRGs) in OC [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Identification and Validation of a Novel Prognostic Signature Based on Ferroptosis-Related Genes in Ovarian Cancer

2023

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Background: Ovarian cancer is the most lethal gynecological tumor, with a poor prognosis due to the lack of early symptoms, resistance to chemotherapy, and recurrence. Ferroptosis belongs to the regulated cell death family, and is characterized by iron-dependent processes. Here, comprehensive bioinformatics analysis was applied to explore a valuable prognostic model based on ferroptosis-related genes, which was further validated in clinical OC samples. Methods: mRNA data of normal and ovarian tumor samples were obtained separately from the GTEx and TCGA databases. The least absolute shrinkage and selection operator (LASSO) cox regression was applied to construct the prognostic model based on ferroptosis-associated genes. Expression of ALOX12 in OC cell lines, as well as cell functions, including proliferation and migration, were examined. Finally, the prognostic efficiency of the model was assessed in the clinical tissues of OC patients. Results: A gene signature consisting of ALOX12, RB1, DNAJB6, STEAP3, and SELENOS was constructed. The signature divided TCGA, ICGC, and GEO cohorts into high-risk and low-risk groups separately. Receiver operating characteristic (ROC) curves and independent prognostic factor analysis were carried out, and the prognostic efficacy was validated. The expression levels of ALOX12 in cell lines were examined. Inhibition of ALOX12 attenuated cell proliferation and migration in HEY cells. Moreover, the prognostic value of ALOX12 expression was examined in clinical samples of OC patients. Conclusion: This work constructed a novel ferroptosis-associated gene model. Furthermore, the clinical predictive role of ALOX12 was identified in OC patients, suggesting that ALOX12 might act as a potential prognostic tool and therapeutic target for OC patients.

show abstract

UCP1 modulates immune infiltration level and survival outcome in ovarian cancer patients

Cited by 7 publications

References 33 publications

Oxidative Stress and ROS Link Diabetes and Cancer

Oxidative Stress and ROS Link Diabetes and Cancer

Oxidative Stress and ROS Linking Diabetes and Cancer

Identification and Validation of a Novel Prognostic Signature Based on Ferroptosis-Related Genes in Ovarian Cancer

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