Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer

Yang, Hui; Hu, Yiren; Weng, Mingzhe; Liu, Xiaocen; Wan, Ping; Hu, Ye; Moody, M. Anthony; Zhang, Yan; Xia, Hongping; Lv, Kun

doi:10.1016/j.jare.2021.10.001

Cited by 129 publications

(88 citation statements)

References 47 publications

(60 reference statements)

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“…To further study the influence of dysfunctional SM on the TIME of OS patients and its predictive significance in OS patients, a prognostic model derived from SM-relevant genes was constructed and verified in the validation cohort. In our model, all three genes identified were associated with tumor initiation and progression (26)(27)(28). CBS encodes a homotetrameric enzyme that catalyzes the first step in the transsulfuration pathway and converses the homocysteine to cystathionine, which is associated with various stomach, liver, and ovarian cancers and influences immune evasion (29).…”

Section: A B D Cmentioning

confidence: 97%

Dissecting the effect of sphingolipid metabolism gene in progression and microenvironment of osteosarcoma to develop a prognostic signature

et al. 2022

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Sphingolipid metabolism (SM) fuels tumorigenesis and the malignant progression of osteosarcoma (OS), which leads to an unfavorable prognosis. Elucidating the molecular mechanisms underlying SM in osteosarcoma and developing a SM-based prognostic signature could be beneficial in the clinical setting. This study included 88 frozen OS samples to recognize the vital SM-relevant genes in the development of OS utilizing univariate Cox regression. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was conducted on the SM- relevant genes to minimize the risk of overfitting. The prognostic signature was generate utilizing the multivariable Cox regression analysis and was verified in the validation cohort. Moreover, cellular and molecular mechanisms associated with SM have an unfavorable prognosis for OS patients and have been widely studied. Resultantly, an SM-based prognostic risk model was established according to critical prognostic genes (CBS, GLB1, and HACD1), which had an excellent ability to predict the prognosis of OS patients (AUC for the train cohort was 0.887 and AUC for validation cohort was 0.737). The high-risk OS patients identified based on this prognostic signature had significantly poor immune microenvironment, indicated by significantly low immune score (mean=216.290 ± 662.463), reduced infiltrations of 25 immune cells, including NK cells (LogFC= -0.3597), CD8+T cells ((LogFC=-0.2346), Cytolytic activity ((LogFC=-0.1998), etc. The immunosuppressive microenvironment could be due to dysregulated SM of glycolipids. Further, a nomogram was constructed by integrating the SM-based prognostic signature and clinical paraments to facilitate clinical application. The nomogram could accurately predict the prognosis of OS invalids. Collectively, this study clarified the function of SM in the development of OS and helped develop a tool for risk stratification based on SM-related genes with application in clinical settings. The results of our study will aid in identifying high-risk patients and provide individualized treatments.

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Section: A B D Cmentioning

confidence: 97%

Dissecting the effect of sphingolipid metabolism gene in progression and microenvironment of osteosarcoma to develop a prognostic signature

et al. 2022

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Section: Clinical Outcomes and Potential Therapies Prediction Of Subg...mentioning

confidence: 99%

“…LncRNA-PMAN was upregulated in GC cells and inhibited Erastin- and RSL3-induced ferroptosis, leading to poor prognosis and peritoneal metastasis [ 22 ]. A hypoxia-induced lncRNA-CBSLR could protect GC cells from ferroptosis, which could contribute to chem-resistance in GC patients [ 23 ]. Considering the tight relationship among ferroptosis, lncRNA, and GC, we constructed a molecular signature based on the ferroptosis-related lncRNAs (FRLs) for GC patients in this study, aiming to help the prognosis prediction of GC.…”

Section: Introductionmentioning

confidence: 99%

Clinical outcomes and potential therapies prediction of subgroups based on a ferroptosis-related long non-coding RNA signature for gastric cancer

Geng

Qian

Zhang

et al. 2022

Aging

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Background: Gastric cancer (GC) is one of the most aggressive malignant tumors worldwide. Ferroptosis is a kind of iron-dependent cell death, which is proved to be closely related to tumor progression. In this study, we aim at constructing a ferroptosis-related lncRNAs signature to predict the prognosis of GC and explore potential therapies. Methods: Ferroptosis-Related LncRNAs Signature for GC patients (FRLSG) was constructed through univariate Cox regression, the LASSO algorithm, and multivariate Cox regression. Kaplan-Meier analysis, receiver operating characteristic curves, and risk score plot were applied to verify the predictive power of FRLSG. Gene Set Enrichment Analysis (GSEA) and immune infiltration analyses were conducted to explore the potential clinical value of the FRLSG. In addition, drug sensitivity prediction was applied to identify chemotherapeutic drugs with potential therapeutic effect. Results: Five ferroptosis-related lncRNAs (AC004816.1, AC005532.1, LINC01357, AL355574.1 and AL049840.4) were identified to construct FRLSG, whose expression level in GC were confirmed by experimental validation. Kaplan-Meier curve and ROC curve proved the reliability and effectiveness of the FRLSG in predicting the prognosis for GC patients. Several immune-related pathways were enriched in the high-FRLSG group, and further immune infiltration analyses demonstrated the high immune infiltration status of the high-FRLSG group. In addition, 19 and 24 candidate drugs with potential therapeutic effect were identified for the high-and low-FRLSG groups, respectively. Conclusions: FRLSG was an effective tool in predicting the prognosis of GC, which might help to prioritize potential therapeutics for GC patients.

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“…4-HNE is currently considered a major bioactive marker of lipid peroxidation and a signalling molecule involved in the regulation of transcription factors sensitive to stress, such as nuclear factor erythroid 2-related factor 2 (Nrf2), in cell proliferation, differentiation, and death [ 25 ]. In ferroptosis, MDA and 4-HNE are reliable markers of oxidative stress-induced lipid peroxidation in cancer [ 28 ], AD [ 29 ], and acute lung injury [ 30 ].…”

Section: Main Characteristics Of Ferroptosismentioning

confidence: 99%

The Role Played by Ferroptosis in Osteoarthritis: Evidence Based on Iron Dyshomeostasis and Lipid Peroxidation

Zhang

et al. 2022

Antioxidants

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Ferroptosis, a recently discovered regulated cell death modality, is characterised by iron-dependent accumulation of lipid hydroperoxides, which can reach lethal levels but can be specifically reversed by ferroptosis inhibitors. Osteoarthritis (OA), the most common degenerative joint disease, is characterised by a complex pathogenesis involving mechanical overload, increased inflammatory mediator levels, metabolic alterations, and cell senescence and death. Since iron accumulation and oxidative stress are the universal pathological features of OA, the role played by ferroptosis in OA has been extensively explored. Increasing evidence has shown that iron dyshomeostasis and lipid peroxidation are closely associated with OA pathogenesis. Therefore, in this review, we summarize recent evidence by focusing on ferroptotic mechanisms and the role played by ferroptosis in OA pathogenesis from the perspectives of clinical findings, animal models, and cell research. By summarizing recent research advances that characterize the relationship between ferroptosis and OA, we highlight avenues for further research and potential therapeutic targets.

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Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer

Cited by 129 publications

References 47 publications

Dissecting the effect of sphingolipid metabolism gene in progression and microenvironment of osteosarcoma to develop a prognostic signature

Dissecting the effect of sphingolipid metabolism gene in progression and microenvironment of osteosarcoma to develop a prognostic signature

Clinical outcomes and potential therapies prediction of subgroups based on a ferroptosis-related long non-coding RNA signature for gastric cancer

The Role Played by Ferroptosis in Osteoarthritis: Evidence Based on Iron Dyshomeostasis and Lipid Peroxidation

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