System analysis based on the cancer–immunity cycle identifies ZNF207 as a novel immunotherapy target for hepatocellular carcinoma

Wang, Xu; Zhou, Tao; Chen, Xingyi; Wang, Yu; Ding, Yushi; Tu, Haoyang; Gao, Shengyang; Wang, Haoyu; Tang, Xin‐Ying; Yang, Yong

doi:10.1136/jitc-2021-004414

Cited by 15 publications

(14 citation statements)

References 46 publications

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“…Meanwhile, plasma indoleamine 2,3-dioxygenase activity correlates with the amount of the human immunodeficiency virus reservoir in patients receiving antiretroviral therapy. 43 , 44 In brief, we hypothesize that CD69 may influence the development of Th17 cells or the metabolic route and that ZNF207 influences the transcription of IDO1 and the synthesis of kynurenine, resulting in CD4 + T cell exhaustion and immunological non-response in HIV-infected patients. We verified the expression of these two genes in the blood of INRs and IRs, and additional experimental research is required to understand their biological processes.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Diagnostic Genes of HIV-Infected Immunological Non-Responders on Bioinformatics Analysis

Ding¹,

Cheng²,

Zhang³

et al. 2023

JIR

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Purpose HIV-infected immunological non-responders (INRs) failed to achieve the normalization of CD4 + T cell counts despite their undetectable viral load. INRs have an increased risk of clinical progressions of Acquired Immunodeficiency Syndrome (AIDS) and non-AIDS events, accompanied by higher mortality rates than immunological responders (IRs). This study aimed to discover the genes, which help to distinguish INRs from IRs and explore the possible mechanism of INRs. Methods Screening DEGs between INRs and IRs using GEO microarray dataset GSE143742. DEG biological functions were investigated using GO and KEGG analysis. DEGs and WGCNA linked modules were intersected to find common genes. Key genes were identified using SVM-RFE and LASSO regression models. ROC analysis was done to evaluate key gene diagnostic effectiveness using GEO database dataset GSE106792. Cytoscape created a miRNA-mRNA-TF network for diagnostic genes. CIBERSORT and flow cytometry examined the INRs and IRs immune microenvironments. In 10 INR and 10 IR clinical samples, diagnostic gene expression was verified by RT-qPCR and Western blot. Results We obtained 190 DEGs between the INR group and IR group. Functional enrichment analysis found a significant enrichment in mitochondria and apoptosis-related pathways. CD69 and ZNF207 were identified as potential diagnostic genes. CD69 and ZNF207 shared a transcription factor, NCOR1, in the miRNA-mRNA-TF network. Immune microenvironment analysis by CIBERSORT showed that IRs had a higher level of resting memory CD4 + T cells, lower level of activated memory CD4 + T cells and resting dendritic cells than INRs, as confirmed by flow cytometry analysis. In addition, CD69 and ZNF207 were correlated with immune cells. Experiments confirmed the expression of the diagnostic genes in INRs and IRs. Conclusion CD69 and ZNF207 were identified as potential diagnostic genes to discriminate INRs from IRs. Our findings offered new clues to diagnostic and therapeutic targets for INRs.

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Section: Discussionmentioning

confidence: 99%

Identification of Potential Diagnostic Genes of HIV-Infected Immunological Non-Responders on Bioinformatics Analysis

Ding¹,

Cheng²,

Zhang³

et al. 2023

JIR

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“…The proportions of 22 immune cells were calculated using the CIBERSORT algorithm 26 . In addition, the activation data of the 7‐step antitumor immunity cycle was downloaded from the TIP database 27 …”

Section: Methodsmentioning

confidence: 99%

“…26 In addition, the activation data of the 7-step antitumor immunity cycle was downloaded from the TIP database. 27…”

Section: Immune Infiltration Analysismentioning

confidence: 99%

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m7G‐related genes—NCBP2 and EIF4E3 determine immune contexture in head and neck squamous cell carcinoma by regulating CCL4/CCL5 expression

Zhao

Ying

et al. 2023

Molecular Carcinogenesis

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Aberrant N 7 -methylguanosine (m7G) levels closely correlate with tumor genesis and progression. NCBP2 and EIF4E3 are two important m7G-related cap-binding genes.This study aimed to identify the relationship between the EIF4E3/NCBP2 function and immunological characteristics of head and neck squamous cell carcinoma (HNSCC). Hierarchical clustering was employed in classifying HNSCC patients into two groups based on the expressions of NCBP2 and EIF4E3. The differentially expressed genes were identified between the two groups, and GO functional enrichment was subsequently performed. Weighted gene co-expression network analysis was conducted to identify the hub genes related to EIF4E3/NCBP2 expression and immunity. The differential infiltration of immune cells and the response to immunotherapy were compared between the two groups. Single-cell sequence and trajectory analyses were performed to predict cell differentiation and display the expression of EIF4E3/NCBP2 in each state. In addition, quantitative real-time PCR, spatial transcriptome analysis, transwell assay, and western blotting were conducted to verify the biological function of EIF4E3/NCBP2. Here, group A showed a higher EIF4E3 expression and a lower NCBP2 expression, which had higher immune scores, proportion of most immune cells, immune activities, expression of immunomodulatory targets, and a better response to cancer immunotherapy.Besides, 56 hub molecules with notable immune regulation significance were identified. A risk model containing 17 hub genes and a prognostic nomogram was successfully established. Moreover, HNSCC tissues had a lower EIF4E3 expression and a higher NCBP2 expression than normal tissues. NCBP2 and EIF4E3 played a vital role in the differentiation of monocytes. Furthermore, the expression of CCL4/CCL5 can be regulated via EIF4E3 overexpression and NCBP2 knockdown. Collectively,

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“…A phase transition of BuGZ promotes microtubule polymerization and spindle apparatus assembly, which is critical for activation of the mitotic kinase AurA [ 37 , 38 ]. In addition, Bub3 and BuGZ are also implicated in the occurrence of cancer [ 39 – 42 ].…”

Section: Introductionmentioning

confidence: 99%

A role for the mitotic proteins Bub3 and BuGZ in transcriptional regulation of catalase-3 expression

Zhou

Shen

et al. 2022

PLoS Genet

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The spindle assembly checkpoint factors Bub3 and BuGZ play critical roles in mitotic process, but little is known about their roles in other cellular processes in eukaryotes. In aerobic organisms, transcriptional regulation of catalase genes in response to developmental or environmental stimuli is necessary for redox homeostasis. Here, we demonstrate that Bub3 and BuGZ negatively regulate cat-3 transcription in the model filamentous fungus Neurospora crassa. The absence of Bub3 caused a significant decrease in BuGZ protein levels. Our data indicate that BuGZ and Bub3 interact directly via the GLEBS domain of BuGZ. Despite loss of the interaction, the amount of BuGZ mutant protein negatively correlated with the cat-3 expression level, indicating that BuGZ amount rather than Bub3-BuGZ interaction determines cat-3 transcription level. Further experiments demonstrated that BuGZ binds directly to the cat-3 gene and responses to cat-3 overexpression induced by oxidative stresses. However, the zinc finger domains of BuGZ have no effects on DNA binding, although mutations of these highly conserved domains lead to loss of cat-3 repression. The deposition of BuGZ along cat-3 chromatin hindered the recruitment of transcription activators GCN4/CPC1 and NC2 complex, thereby preventing the assembly of the transcriptional machinery. Taken together, our results establish a mechanism for how mitotic proteins Bub3 and BuGZ functions in transcriptional regulation in a eukaryotic organism.

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System analysis based on the cancer–immunity cycle identifies ZNF207 as a novel immunotherapy target for hepatocellular carcinoma

Cited by 15 publications

References 46 publications

Identification of Potential Diagnostic Genes of HIV-Infected Immunological Non-Responders on Bioinformatics Analysis

Identification of Potential Diagnostic Genes of HIV-Infected Immunological Non-Responders on Bioinformatics Analysis

m7G‐related genes—NCBP2 and EIF4E3 determine immune contexture in head and neck squamous cell carcinoma by regulating CCL4/CCL5 expression

A role for the mitotic proteins Bub3 and BuGZ in transcriptional regulation of catalase-3 expression

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