The characteristics of the ancient cell death suppressor, TMBIM6, and its related signaling pathways after endoplasmic reticulum stress

Doycheva, Desislava; Kaur, Harpreet; Tang, Jiping; Zhang, Junyi

doi:10.1002/jnr.24434

Cited by 11 publications

(7 citation statements)

References 78 publications

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“…TMBIM6 is evolutionarily conserved and predominantly localized in the endoplasmic reticulum. It has been implicated in various cellular processes, including anti‐apoptotic, anti‐inflammatory, and anti‐oxidative functions 37 . Moreover, TMBIM6 expression has been noted to vary across diverse tissues and developmental stages, suggesting its potential involvement in tissue homeostasis and developmental processes.…”

Section: Discussionmentioning

confidence: 99%

Characteristics and significance of programmed cell death‐related gene expression signature in skin cutaneous melanoma

Wu,

Chen,

et al. 2024

Skin Research and Technology

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BackgroundProgrammed cell death (PCD) pathways play crucial roles in the pathogenesis of skin cutaneous melanoma (SKCM). Understanding their prognostic significance and clinical implications is imperative for the development of personalized treatment strategies.MethodsA total of 1466 PCD‐related genes were analyzed using data from The Cancer Genome Atlas (TCGA)‐SKCM cohort (n = 353). Prognostic cell death index (CDI) was established and validated through survival analysis and predictive modeling. Functional enrichment, protein‐protein interaction (PPI), consensus clustering, and tumor microenvironment assessment and drug sensitivity analysis were performed to elucidate the biological and clinical relevance of CDI.ResultsCDI effectively stratified SKCM patients into high and low‐risk groups, demonstrating significant differences in survival outcomes. It exhibited predictive value for survival at 1, 3, and 5 years. The concordance index (C‐index) was 0.794 in the training set, and 0.792 and 0.821 in the internal and external validation sets, respectively. The corresponding area under curve (AUC) was all above 0.75 in these data sets. Functional enrichment analysis revealed significant associations with immune response and inflammatory processes. PPI analysis identified key molecular modules associated with apoptosis and chemokine signaling. Consensus clustering unveiled three discernible subtypes demonstrating notable disparities in survival outcomes based on CDI expression profiles. Assessment of the tumor microenvironment highlighted correlations with immune cell infiltration such as M1 macrophages and T cells. Drug sensitivity analysis indicated tight correlations between CDI levels and response to immunotherapy.ConclusionOur comprehensive analysis establishes the prognostic significance of PCD‐related genes in SKCM. CDI emerges as a promising prognostic biomarker, offering insights into tumor biology and potential implications for personalized treatment strategies. Further validation and clinical integration of CDI are warranted to improve SKCM management and patient outcomes.

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Section: Discussionmentioning

confidence: 99%

Characteristics and significance of programmed cell death‐related gene expression signature in skin cutaneous melanoma

Wu,

Chen,

et al. 2024

Skin Research and Technology

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“…It regulates ER calcium homeostasis, impacting stimulated calcium release and calcium-mediated cell death. TMBIM6 negatively modulates ER calcium release and acts as an ani-apoptotic factor under conditions of the accumulation of misfolded proteins in the ER lumen [ 35 , 36 ]. Moreover, TMBIM6 protects the cells from the ER dysfunction, but in our study TMBIM6 expression did not correspond to CANX and PDIA4 expression.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Profile of Genes Encoding Proteins Involved in Pathogenesis of Sjögren’s Syndrome Related Xerostomia—Molecular and Clinical Trial

Błochowiak

Celichowski

Kempisty

et al. 2020

JCM

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Sjögren’s syndrome (SS) is characterized by xerostomia. We aimed to investigate and compare gene expressions in the labial salivary glands of SS patients with xerostomia SS (sicca) and without xerostomia SS (non-sicca) and of healthy subjects (HS) by means of microarray analysis, and to find genes involved in xerostomia. The study group comprised 11 SS patients (3 SS (sicca) and 8 SS (non-sicca)) and 9 HS. The relative gene expression changes were validated with RT-qPCR in the larger study group. Among the differently expressed genes belonging to the “secretion” ontology group with a fold change >2 and with a p value < 0.05, the Transmembrane P24 Trafficking Protein 10 (TMED10), Protein Disulfide Isomerase Family A Member 4 (PDIA4), Calnexin (CANX), Amyloid Beta Precursor Protein (APP), and Transmembrane BAX Inhibitor Motif Containing 6 (TMBIM6) gene expressions in both SS (sicca) and SS (non-sicca) groups were lower than in HS. Significant correlations were observed between TMED10, PDIA4, and CANX gene expression in SS (sicca) patients compared to the controls. There were no differences between the SS (sicca) and SS (non-sicca) study groups in the expression of the aforementioned genes. Results indicate their role in the endoplasmic reticulum system, their overlapping function and the loss of the APP neuroprotective function in xerostomia. It has a multifactorial origin and can be triggered by disturbances to the various signaling pathways in saliva secretion.

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“…HIF regulates various genes, including some associated with energy metabolism, but has also been recently shown to contribute to epigenetic changes. Similarly, endoplasmic reticulum (ER) stress causes oxidative damage and cell death (Doycheva, Kaur, Tang, & Zhang, ). The role of Bax Inhibitor‐1 (BI‐1), an evolutionarily conserved protein encoded by the Transmembrane Bax inhibitor Motif, has been proposed to be protective from ER stress.…”

Section: Edema Neuroinflammation and The Immune System In Secondarymentioning

confidence: 99%

“…The role of Bax Inhibitor‐1 (BI‐1), an evolutionarily conserved protein encoded by the Transmembrane Bax inhibitor Motif, has been proposed to be protective from ER stress. The neuroprotective properties of BI‐1 are examined as a potential drug intervention (Doycheva et al, ). In the last decade, noncoding RNAs have been investigated as having a potential role in gene regulation in secondary injury.…”

Section: Edema Neuroinflammation and The Immune System In Secondarymentioning

confidence: 99%

17th international conference on Brain Edema and Cellular Injury

Badaut

Zhang

2019

J of Neuroscience Research

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The characteristics of the ancient cell death suppressor, TMBIM6, and its related signaling pathways after endoplasmic reticulum stress

Cited by 11 publications

References 78 publications

Characteristics and significance of programmed cell death‐related gene expression signature in skin cutaneous melanoma

Characteristics and significance of programmed cell death‐related gene expression signature in skin cutaneous melanoma

Transcriptomic Profile of Genes Encoding Proteins Involved in Pathogenesis of Sjögren’s Syndrome Related Xerostomia—Molecular and Clinical Trial

17th international conference on Brain Edema and Cellular Injury

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