Casp8 acts through A20 to inhibit PD‐L1 expression: The mechanism and its implication in immunotherapy

Zou, Jiahuan; Xiao, Hong‐Wei; Zhang, Chenliang; Xu, Huanji; Tang, Qiulin; Zhu, Gongmin; Li, Jielang; Bi, Feng

doi:10.1111/cas.14932

Cited by 20 publications

(15 citation statements)

References 50 publications

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“…CASP8 is an apical caspase protease that mediates both pro-death and pro-survival functions [ 38 , 39 ]. CASP8 upregulates TNFAIP3 expression to promote PD-L1 ubiquitination and degradation [ 40 ]. Moreover, depression of PD-L1 may induce psoriasis [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Chromatin accessibility and transcriptome integrative analysis revealed AP-1-mediated genes potentially modulate histopathology features in psoriasis

Tang

Zhang

et al. 2022

Clin Epigenet

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Background Psoriasis is a chronic and hyperproliferative skin disease featured by hyperkeratosis with parakeratosis, Munro micro-abscess, elongation of rete pegs, granulosa thinning, and lymphocyte infiltration. We previously profiled gene expression and chromatin accessibility of psoriatic skins by transcriptome sequencing and ATAC-seq. However, integrating both of these datasets to unravel gene expression regulation is lacking. Here, we integrated transcriptome and ATAC-seq of the same psoriatic and normal skin tissues, trying to leverage the potential role of chromatin accessibility and their function in histopathology features. Results By inducing binding and expression target analysis (BETA) algorithms, we explored the target prediction of transcription factors binding in 15 psoriatic and 19 control skins. BETA identified 408 upregulated genes (rank product < 0.01) and 133 downregulated genes linked with chromatin accessibility. We noticed that cumulative fraction of genes in upregulation group was statistically higher than background, while that of genes in downregulation group was not significant. KEGG pathway analysis showed that the upregulated 408 genes were enriched in TNF, NOD, and IL-17 signaling pathways. In addition, the motif module in BETA suggested the 57 upregulated genes are targeted by transcription factor AP-1, indicating that increased chromatin accessibility facilitated the binding of AP-1 to the target regions and further induced expression of relevant genes. Among these genes, SQLE, STRN, EIF4, and MYO1B expression was increased in patients with hyperkeratosis, parakeratosis, and acanthosis thickening. Conclusions In summary, with the advantage of BETA, we identified a series of genes that contribute to the disease pathogenesis, especially in modulating histopathology features, providing us with new clues in treating psoriasis.

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Section: Discussionmentioning

confidence: 99%

Chromatin accessibility and transcriptome integrative analysis revealed AP-1-mediated genes potentially modulate histopathology features in psoriasis

Tang

Zhang

et al. 2022

Clin Epigenet

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“…Multiple modes of cell death may co-exist and interact with each other during the disease process. Previous articles have identified CASP8 as a “molecular switch” that controls apoptosis, pyroptosis and necroptosis ( 32 ). GZMA and NLRP6 are also involved in the inflammatory cascade of apoptosis ( 33 , 34 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical Implications of Necroptosis Genes Expression for Cancer Immunity and Prognosis: A Pan-Cancer Analysis

Su²,

Chen³

et al. 2022

Front. Immunol.

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BackgroundNecroptosis, a form of programmed cell death, is increasingly being investigated for its controversial role in tumorigenesis and progression. Necroptosis suppresses tumor formation and tumor development by killing tumor cells; however, the necrotic cells also promote tumor formation and tumor development via the immunosuppressive effect of necroptosis and inflammatory response caused by cytokine release. Thus, the exact mechanism of necroptosis in pan-cancer remains unknown.MethodsThe data of 11,057 cancer samples were downloaded from the TCGA database, along with clinical information, tumor mutation burden, and microsatellite instability information of the corresponding patients. We used the TCGA data in a pan-cancer analysis to identify differences in mRNA level as well as single nucleotide variants, copy number variants, methylation profiles, and genomic signatures of miRNA-mRNA interactions. Two drug datasets (from GDSC, CTRP) were used to evaluate drug sensitivity and resistance against necroptosis genes.ResultsNecroptosis genes were aberrantly expressed in various cancers. The frequency of necroptosis gene mutations was highest in lung squamous cell carcinoma. Furthermore, the correlation between necroptosis gene expression in the tumor microenvironment and immune cell infiltration varied for different cancers. High necroptosis gene expression was found to correlate with NK, Tfh, Th1, CD8_T, and DC cells. These can therefore be used as biomarkers to predict prognosis. By matching gene targets with drugs, we identified potential candidate drugs.ConclusionOur study showed the genomic alterations and clinical features of necroptosis genes in 33 cancers. This may help clarify the link between necroptosis and tumorigenesis. Our findings may also provide new approaches for the clinical treatment of cancer.

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“…Fritsch et al established that caspase-8 functions as the pyroptotic (17). The CASP8 gene is a critical cancer susceptible gene, as shown by numerous researches examining a variety of tumor forms, such as ovarian cancer, lung, prostate, and breast (18)(19)(20). Soung et al discovered that the CASP8 gene is commonly altered in HCC and that this mutation could result in the loss of the cell death role of CASP8 gene, thereby leading to the occurrence and progression of HCC (21).…”

Section: Discussionmentioning

confidence: 99%

A newly identified pyroptosis-related gene signature for predicting prognosis of patients with hepatocellular cancer

Shen¹,

Jiang²,

Hu³

et al. 2022

Transl Cancer Res TCR

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Background: Hepatocellular carcinoma (HCC) is a very heterogeneous illness, making prognosis prediction a huge problem. Pyroptosis, which has recently been shown to be an inflammatory type of programmed cell death, is involved in HCC. Nevertheless, the role of pyroptosis-related genes in HCC has not been fully elucidated. Thus, this study aimed to construct a prognostic signature based on pyroptosisrelated genes for HCC. Methods:The messenger RNA expression patterns of HCC patients, as well as the accompanying clinical information, were retrieved from The Cancer Genome Atlas (TCGA) database for this research. After differentially expressed pyroptosis-related Gene in tumor and normal groups were identified, Cox regression analyses were performed to construct a prognostic signature which was then assessed through independent prognostic analysis.Results: A signature consisting of four genes (CASP8, GSDME, NOD2, and PLCG1) was constructed to predict overall survival (OS) for HCC. The signature was identified to be independent by the cox regression analysis and obtained the largest area under the receiver operating characteristic (ROC) curve (AUC) was 0.691, 0.628, and 0.632 for survival at 1, 2, and 3 years, respectively.Conclusions: we discovered that the levels of pyroptosis-related genes expression differed across HCC patients and were associated with both survival and prognosis. This suggested that targeting pyroptosis as a treatment strategy for HCC may be a viable option.

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Casp8 acts through A20 to inhibit PD‐L1 expression: The mechanism and its implication in immunotherapy

Cited by 20 publications

References 50 publications

Chromatin accessibility and transcriptome integrative analysis revealed AP-1-mediated genes potentially modulate histopathology features in psoriasis

Chromatin accessibility and transcriptome integrative analysis revealed AP-1-mediated genes potentially modulate histopathology features in psoriasis

Clinical Implications of Necroptosis Genes Expression for Cancer Immunity and Prognosis: A Pan-Cancer Analysis

A newly identified pyroptosis-related gene signature for predicting prognosis of patients with hepatocellular cancer

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