COPZ1 depletion in thyroid tumor cells triggers type I IFN response and immunogenic cell death

Marco, Tiziana Di; Bianchi, Francesca; Sfondrini, Lucia; Todoerti, Katia; Bongarzone, Italia; Maffioli, Elisa; Tedeschi, Gioacchino; Mazzoni, Mara; Pagliardini, Sonia; Pellegrini, Sandra; Neri, Antonino; Anania, Maria Chiara; Greco, Angela

doi:10.1016/j.canlet.2020.02.011

Cited by 10 publications

(7 citation statements)

References 65 publications

(64 reference statements)

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“…When looking at genes that showed differential imbalance between the autoimmunity related phenogroup 2 and the rest of the cohort, four out of the top five most significant hits were related to inflammatory processes like programmed cell death and autophagy (Supplementary Table 2) [20][21][22][23] . One of these genes, APIP, has been shown to carry out a cardioprotective role in the inflammatory process following myocardial infarction 20 .…”

Section: Discussionmentioning

confidence: 99%

Allele-specific expression analysis for complex genetic phenotypes applied to a unique dilated cardiomyopathy cohort

Beek

Verdonschot

Derks

et al. 2023

Sci Rep

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Allele-specific expression (ASE) analysis detects the relative abundance of alleles at heterozygous loci as a proxy for cis-regulatory variation, which affects the personal transcriptome and proteome. This study describes the development and application of an ASE analysis pipeline on a unique cohort of 87 well phenotyped and RNA sequenced patients from the Maastricht Cardiomyopathy Registry with dilated cardiomyopathy (DCM), a complex genetic disorder with a remaining gap in explained heritability. Regulatory processes for which ASE is a proxy might explain this gap. We found an overrepresentation of known DCM-associated genes among the significant results across the cohort. In addition, we were able to find genes of interest that have not been associated with DCM through conventional methods such as genome-wide association or differential gene expression studies. The pipeline offers RNA sequencing data processing, individual and population level ASE analyses as well as group comparisons and several intuitive visualizations such as Manhattan plots and protein–protein interaction networks. With this pipeline, we found evidence supporting the case that cis-regulatory variation contributes to the phenotypic heterogeneity of DCM. Additionally, our results highlight that ASE analysis offers an additional layer to conventional genomic and transcriptomic analyses for candidate gene identification and biological insight.

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Section: Discussionmentioning

confidence: 99%

Allele-specific expression analysis for complex genetic phenotypes applied to a unique dilated cardiomyopathy cohort

Beek

Verdonschot

Derks

et al. 2023

Sci Rep

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“…Therefore, exploring the molecular and regulatory mechanisms related to tumor immunity is beneficial for increasing the effectiveness of cancer immunotherapy and predict the prognosis of patients. An earlier investigation discovered that COPZ1 knockdown might boost the release of several pro-inflammatory cytokines, which would then accelerate dendritic cell maturation and heighten the cytotoxic T cell response [ 14 ]. Based on our KEGG pathway GSEA analysis, we found a close correlation between COPZ1 and the tumor immune response pathways, such as TNF signaling pathway, Chemokine signaling pathway, T cell receptor signaling pathway, Toll-like receptor signaling pathway, NOD-like receptor signaling pathways, which indicated that COPZ1 may involve in the tumor immunity.…”

Section: Discussionmentioning

confidence: 99%

“…Depletion of COPZ1 can lead to thyroid tumor cell death both in vitro and in vivo [ 13 ]. Besides, Silencing COPZ1 causes the endoplasmic reticulum (ER) stress to increase and the type I IFN pathway activated, and then promotes the secretion of a variety of inflammatory molecules and enhances anti-tumor immunity in thyroid cancer [ 14 ]. Another research found that knockdown of COPZ1 leads to ferroptosis by inducing NCOA4-mediated autophagy in human GBM cells [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Pan-Cancer Analysis of the Regulation and Prognostic Effect of Coat Complex Subunit Zeta 1

Hong

Xia

Sun

et al. 2023

Genes

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The Coatomer protein complex Zeta 1 (COPZ1) has been reported to play an essential role in maintaining the survival of some types of tumors. In this study, we sought to explore the molecular characteristics of COPZ1 and its clinical prognostic value through a pan-cancers bioinformatic analysis. We found that COPZ1 was extremely prevalent in a variety of cancer types, and high expression of COPZ1 was linked to poor overall survival in many cancers, while low expression in LAML and PADC was correlated with tumorigenesis. Besides, the CRISPR Achilles’ knockout analysis revealed that COPZ1 was vital for many tumor cells’ survival. We further demonstrated that the high expression level of COPZ1 in tumors was regulated in multi-aspects, including abnormal CNV, DNA-methylation, transcription factor and microRNAs. As for the functional exploration of COPZ1, we found a positive relationship between COPZ1’s expression and stemness and hypoxia signature, especially the contribution of COPZ1 on EMT ability in SARC. GSEA analysis revealed that COPZ1 was associated with many immune response pathways. Further investigation demonstrated that COPZ expression was negatively correlated with immune score and stromal score, and low expression of COPZ1 has been associated to more antitumor immune cell infiltration and pro-inflammatory cytokines. The further analysis of COPZ1 expression and anti-inflammatory M2 cells showed a consistent result. Finally, we verified the expression of COPZ1 in HCC cells, and proved its ability of sustaining tumor growth and invasion with biological experiments. Our study provides a multi-dimensional pan-cancer analysis of COPZ and demonstrates that COPZ1 can serve as both a prospective target for the treatment of cancer and a prognostic marker for a variety of cancer types.

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“…The link between ICD and the type-I interferon pathway is well established [169]. COPZ1 deficiency triggers type-I IFN responses and immunogenic cell death in thyroid tumor cells [170]. Immunotherapy, represented by immune checkpoint blockade, has changed the cancer treatment paradigm.…”

Section: Other Non-apoptotic Cell Death Mechanisms and Thyroid Diseasementioning

confidence: 99%

Non-Apoptotic Programmed Cell Death in Thyroid Diseases

Qiu

2022

Pharmaceuticals

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Thyroid disorders are among the most common endocrinological conditions. As the prevalence of thyroid diseases increases annually, the exploration of thyroid disease mechanisms and the development of treatments are also gradually improving. With the gradual advancement of therapies, non-apoptotic programmed cell death (NAPCD) has immense potential in inflammatory and neoplastic diseases. Autophagy, pyroptosis, ferroptosis, and immunogenic cell death are all classical NAPCD. In this paper, we have compiled the recent mechanistic investigations of thyroid diseases and established the considerable progress by NAPCD in thyroid diseases. Furthermore, we have elucidated the role of various types of NAPCD in different thyroid disorders. This will help us to better understand the pathophysiology of thyroid-related disorders and identify new targets and mechanisms of drug resistance, which may facilitate the development of novel diagnostic and therapeutic strategies for patients with thyroid diseases. Here, we have reviewed the advances in the role of NAPCD in the occurrence, progression, and prognosis of thyroid diseases, and highlighted future research prospects in this area.

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COPZ1 depletion in thyroid tumor cells triggers type I IFN response and immunogenic cell death

Cited by 10 publications

References 65 publications

Allele-specific expression analysis for complex genetic phenotypes applied to a unique dilated cardiomyopathy cohort

Allele-specific expression analysis for complex genetic phenotypes applied to a unique dilated cardiomyopathy cohort

A Comprehensive Pan-Cancer Analysis of the Regulation and Prognostic Effect of Coat Complex Subunit Zeta 1

Non-Apoptotic Programmed Cell Death in Thyroid Diseases

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