HIF-1α Metabolic Pathways in Human Cancer

Elzakra, Naseim; Kim, Yong

doi:10.1007/978-3-030-51652-9_17

Cited by 39 publications

(23 citation statements)

References 200 publications

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“…To explore the expression distribution of IL-37 and SIGIRR genes in different cell types of the human lung, the Single-Cell Type Atlas part of the Human Protein Atlas was used [ 35 ]. Finally, the effect of IL-37 nucleotide changes or aberrations in expression levels on the differential distribution of various immune cell subsets infiltrating the LUAD tumor was analyzed using the TIMER2.0 webserver [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

“…To analyze the effect of IL-37 nucleotide changes on or the association of IL-37 expression levels with immune cell infiltration of lung tumors, the TIMER2.0 webserver was used [ 36 ]. The “mutation” module was utilized for the investigation of possible differential distribution of macrophages, CD4 + or CD8 + T cells, Tregs, dendritic cells (DCs), neutrophils, B cells, monocytes, NK cells, MDSCs, and endothelial cells in LUAD tumors of patients with IL-37 somatic mutations vs. those without.…”

Section: Methodsmentioning

confidence: 99%

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Aberrant Expression and Prognostic Potential of IL-37 in Human Lung Adenocarcinoma

et al. 2022

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Interleukin-37 (IL-37) is a relatively new IL-1 family cytokine that, due to its immunoregulatory properties, has lately gained increasing attention in basic and translational biomedical research. Emerging evidence supports the implication of this protein in any human disorder in which immune homeostasis is compromised, including cancer. The aim of this study was to explore the prognostic and/or diagnostic potential of IL-37 and its receptor SIGIRR (single immunoglobulin IL-1-related receptor) in human tumors. We utilized a series of bioinformatics tools and -omics datasets to unravel possible associations of IL-37 and SIGIRR expression levels and genetic aberrations with tumor development, histopathological parameters, distribution of tumor-infiltrating immune cells, and survival rates of patients. Our data revealed that amongst the 17 human malignancies investigated, IL-37 exhibits higher expression levels in tumors of lung adenocarcinoma (LUAD). Moreover, the expression profiles of IL-37 and SIGIRR are associated with LUAD development and tumor stage, whereas their high mRNA levels are favorable prognostic factors for the overall survival of patients. What is more, IL-37 correlates positively with a LUAD-associated transcriptomic signature, and its nucleotide changes and expression levels are linked with distinct infiltration patterns of certain cell subsets known to control LUAD anti-tumor immune responses. Our data indicate the potential value of IL-37 and its receptor SIGIRR to serve as biomarkers and/or immune-checkpoint therapeutic targets for LUAD patients. Further, the data highlight the urgent need for further exploration of this cytokine and the underlying pathogenetic mechanisms to fully elucidate its implication in LUAD development and progression.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Aberrant Expression and Prognostic Potential of IL-37 in Human Lung Adenocarcinoma

et al. 2022

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“…Under normoxia, HIF-1α is strictly modulated by an E3 ligase von Hippel-Lindau (VHL), which induces ubiquitination-dependent proteasomal degradation of HIF-1α ( Semenza, 2003 ). Activated HIF-1α translocates into the nucleus and activates targeting genes, which participates in tumor angiogenesis, metastasis, invasion and glucose homeostasis in various cancer cell lines ( Elzakra and Kim, 2021 ; Satija et al, 2021 ). Here, K32 methylation of HIF-1α by SETD7 promotes HIF-1α degradation in the nucleus and thus the inhibited expression of downstream genes in a proline hydroxylation-independent manner.…”

Section: Setd7-mediated Substrate Modifications and Their Role In Cancermentioning

confidence: 99%

The Epigenetic Regulation of Nonhistone Proteins by SETD7: New Targets in Cancer

Chiang

Heng²,

Zhu³

et al. 2022

Front. Genet.

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Epigenetic modifications are essential mechanism by which to ensure cell homeostasis. One such modification is lysine methylation of nonhistone proteins by SETD7, a mono-methyltransferase containing SET domains. SETD7 methylates over 30 proteins and is thus involved in various classical pathways. As such, SETD7 has been implicated in both the basic functions of normal tissues but also in several pathologies, such as cancers. In this review, we summarize the current knowledge of SETD7 substrates, especially transcriptional-related proteins and enzymes, and their putative roles upon SETD7-mediated methylation. We focus on the role of SETD7 in cancers, and speculate on the possible points of intervention and areas for future research.

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“…The aerobic glycolysis is regarded as one of the cancer metabolic hallmarks, which is also called as Warburg effect to build up biomass in the need of highly proliferative cancer cells ( Martínez-Reyes and Chandel, 2021 ). The tumor suppressor p53 inhibits glycolysis by reducing the expression of glucose transporter GLUT1 and downstream glycolytic enzymes, such as hexokinases, glucose-6-phosphate isomerase, etc, while the activations of c-Myc and hypoxia-inducible factor 1α (HIF1α) can induce the transcriptions of these glycolysis-related genes ( Boutelle and Attardi, 2021 ; Elzakra and Kim. 2021 ; Tambay, et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of hexosamine biosynthesis pathway as a novel prognostic signature and its correlation with immune infiltration in bladder cancer

Cui

Feng

Liu

et al. 2022

Front. Mol. Biosci.

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Background: Urinary bladder cancer (UBC) is one of the common urological malignancies, lacking reliable biomarkers to predict clinical outcomes in UBC patients. Thus, it is needed to identify the novel diagnostic/prognostic biomarkers to stratify the high-risk UBC patients. As a shunt pathway of glycolysis, the hexosamine biosynthesis pathway (HBP) has been implicated in carcinogenesis. However, its prognostic value in UBC remains unclear.Methods: The RNA sequencing and mRNA microarray datasets were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus databases. The expression levels of five HBP genes were analyzed in normal and UBC samples, and their associations with stage, grade and survival were plotted. The performance of HBP risk group was evaluated by receiver-operating characteristics (ROC) curve. The HBP signature was generated by Gene Set Variation Analysis (GSVA) and its association with clinicopathological parameters and survival were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out to examine the potential biological functions of HBP using DAVID online tool. The infiltration estimation fraction of immune cells was performed using CIBERSORT-ABS algorithm. Gene set enrichment analysis (GSEA) was used to explore the potential function of HBP in tumor immunoregulation.Results: Four HBP genes were upregulated in UBCs compared to normal tissues in TCGA-BLCA dataset. The upregulation of all five HBP genes was significantly associated with tumor grade and stage of UBC in three independent UBC datasets. The expression of HBP genes predicted poor clinical outcomes in UBC patients in both TCGA-BLCA and GSE13507 datasets. The high-risk group based on HBP genes showed a poor prognosis. Furthermore, HBP signature was positively associated with tumor grade and stage in TCGA-BLCA dataset and with tumor grade, stage, distal metastasis and poor survival in GSE13507 dataset. Interestingly, high-HBP signature group exhibited a high infiltration of immune cells, particularly the macrophage population.Conclusion: We identified that HBP was a promising prognostic biomarker in UBC patients and strongly associated with immune infiltration.

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HIF-1α Metabolic Pathways in Human Cancer

Cited by 39 publications

References 200 publications

Aberrant Expression and Prognostic Potential of IL-37 in Human Lung Adenocarcinoma

Aberrant Expression and Prognostic Potential of IL-37 in Human Lung Adenocarcinoma

The Epigenetic Regulation of Nonhistone Proteins by SETD7: New Targets in Cancer

Identification of hexosamine biosynthesis pathway as a novel prognostic signature and its correlation with immune infiltration in bladder cancer

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