Serine metabolism antagonizes antiviral innate immunity by preventing ATP6V0d2-mediated YAP lysosomal degradation

Shen, Long; Hu, Penghui; Zhang, Yanan; Ji, Zemin; Shan, Xiaonan; Ni, Lina; Na, Ning; Wang, Jing; Tian, He; Shui, Guanghou; Yuan, Yukang; Li, Guoli; Zheng, Hui; Xiang, Yang; Huang, Dandan; Feng, Xiangling; Plewczynski, Dariusz; Liu, Zhe; Wang, Ting; Yu, Qiujing

doi:10.1016/j.cmet.2021.03.006

Cited by 67 publications

(52 citation statements)

References 47 publications

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“…It can be seen from Table S5 that the pathways such as L-serine degradation are significantly activated. Recently, Yu’s team reported that serine metabolism can regulate the innate immunity of antiviral through inhibit YAP lysosomal degradation 27 . It is suggested that HCC is closely related to immunity.…”

Section: Discussionmentioning

confidence: 99%

RNA-seq profiling reveals PBMC RNA as a potential biomarker for hepatocellular carcinoma

Han

Feng

et al. 2021

Sci Rep

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Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and has extremely high morbidity and mortality. Although many existing studies have focused on the identification of biomarkers, little information has been uncovered regarding the PBMC RNA profile of HCC. We attempted to create a profile throughout using expression of peripheral blood mononuclear cell (PBMC) RNA using RNA-seq technology and compared the transcriptome between HCC patients and healthy controls. Seventeen patients and 17 matched healthy controls were included in this study, and PBMC RNA was sequenced from all samples. Sequencing data were analyzed using bioinformatics tools, and quantitative reverse transcription PCR (qRT-PCR) was used for selected validation of DEGs. A total of 1,578 dysregulated genes were found in the PBMC samples, including 1,334 upregulated genes and 244 downregulated genes. GO enrichment and KEGG studies revealed that HCC is closely linked to differentially expressed genes (DEGs) implicated in the immune response. Expression of 6 selected genes (SELENBP1, SLC4A1, SLC26A8, HSPA8P4, CALM1, and RPL7p24) was confirmed by qRT-PCR, and higher sensitivity and specificity were obtained by ROC analysis of the 6 genes. CALM1 was found to gradually decrease as tumors enlarged. Nearly the opposite expression modes were obtained when compared to tumor sequencing data. Immune cell populations exhibited significant differences between HCC and controls. These findings suggest a potential biomarker for the diagnosis of HCC. This study provides new perspectives for liver cancer development and possible future successful clinical diagnosis.

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Section: Discussionmentioning

confidence: 99%

RNA-seq profiling reveals PBMC RNA as a potential biomarker for hepatocellular carcinoma

Han

Feng

et al. 2021

Sci Rep

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“…More recently, type I IFN has been linked to epigenetic regulation in macrophages via control of amino acid metabolism. Type I IFN was shown to suppress the serine-synthesis pathway (SSP), thus negatively impacting on the production of S-adenosyl-methionine (SAM), the only substrate for histone methylation, and eventually deposition of H3K27me3 on gene promoters (Shen et al, 2021). The link between metabolites and chromatin modifiers, and more in general the effects of metabolic reprogramming on macrophage function, have been extensively reviewed Phan et al, 2017;Williams & O'Neill, 2018;Jung et al, 2019).…”

Section: Coordination Of Transcriptional and Metabolic Changesmentioning

confidence: 99%

“…More recently, type I IFN has been linked to epigenetic regulation in macrophages via control of amino acid metabolism. Type I IFN was shown to suppress the serine‐synthesis pathway (SSP), thus negatively impacting on the production of S‐adenosyl‐methionine (SAM), the only substrate for histone methylation, and eventually deposition of H3K27me3 on gene promoters (Shen et al , 2021).…”

Section: Introductionmentioning

confidence: 99%

Integration of transcriptional and metabolic control in macrophage activation

2021

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Macrophages react to microbial and endogenous danger signals by activating a broad panel of effector and homeostatic responses. Such responses entail rapid and stimulus‐specific changes in gene expression programs accompanied by extensive rewiring of metabolism, with alterations in chromatin modifications providing one layer of integration of transcriptional and metabolic regulation. A systematic and mechanistic understanding of the mutual influences between signal‐induced metabolic changes and gene expression is still lacking. Here, we discuss current evidence, controversies, knowledge gaps, and future areas of investigation on how metabolic and transcriptional changes are dynamically integrated during macrophage activation. The cross‐talk between metabolism and inflammatory gene expression is in part accounted for by alterations in the production, usage, and availability of metabolic intermediates that impact the macrophage epigenome. In addition, stimulus‐inducible gene expression changes alter the production of inflammatory mediators, such as nitric oxide, that in turn modulate the activity of metabolic enzymes thus determining complex regulatory loops. Critical issues remain to be understood, notably whether and how metabolic rewiring can bring about gene‐specific (as opposed to global) expression changes.

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“…This protocol describes the analysis of innate immunity induced by vesicular stomatitis virus infection of peritoneal macrophages in vitro and in vivo detection of IFN-β production and lung injury. For complete details on the use and execution of this protocol, please refer to Shen et al. (2021) .…”

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confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Shen et al. (2021) .…”

mentioning

confidence: 99%

In vitro and in vivo evaluation of virus-induced innate immunity in mouse

Shen

Shan

et al. 2021

STAR Protocols

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Summary Innate immunity is the first line of host defense against viral infection. As one of the innate immune cell types, antigen-presenting cells play an important role in the process of antiviral immunity. This protocol describes the analysis of innate immunity induced by vesicular stomatitis virus infection of peritoneal macrophages in vitro and in vivo detection of IFN-β production and lung injury. For complete details on the use and execution of this protocol, please refer to Shen et al. (2021) .

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Serine metabolism antagonizes antiviral innate immunity by preventing ATP6V0d2-mediated YAP lysosomal degradation

Cited by 67 publications

References 47 publications

RNA-seq profiling reveals PBMC RNA as a potential biomarker for hepatocellular carcinoma

RNA-seq profiling reveals PBMC RNA as a potential biomarker for hepatocellular carcinoma

Integration of transcriptional and metabolic control in macrophage activation

In vitro and in vivo evaluation of virus-induced innate immunity in mouse

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