Regulation and action of interferon-stimulated gene 15 in breast cancer cells

Tecalco-Cruz, Ángeles C.; Ramírez-Jarquín, Josué O.; Cruz-Ramos, Eduardo

doi:10.1007/s13577-020-00414-x

Cited by 5 publications

(4 citation statements)

References 61 publications

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“…The ubiquitin domains in ISG15 make it possible for ISG15 to be conjugated to some other proteins via lysine residues. The conjugated ISG15 (ISGylation) has pro-tumorigenic activity, while the extracellular free form has anti-tumorigenic activity in breast cancer [ 84 ] and is being considered as a tumor-associated antigen for cancer immunotherapy [ 85 ]. In OSCC, ISG15 was reported to be upregulated and to affect migration and lymph node metastasis [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide DNA methylation profiling of HPV-negative leukoplakia and gingivobuccal complex cancers

et al. 2023

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Background Gingivobuccal complex oral squamous cell carcinoma (GBC-OSCC) is an aggressive malignancy with high mortality often preceded by premalignant lesions, including leukoplakia. Previous studies have reported genomic drivers in OSCC, but much remains to be elucidated about DNA methylation patterns across different stages of oral carcinogenesis. Results There is a serious lack of biomarkers and clinical application of biomarkers for early detection and prognosis of gingivobuccal complex cancers. Hence, in search of novel biomarkers, we measured genome-wide DNA methylation in 22 normal oral tissues, 22 leukoplakia, and 74 GBC-OSCC tissue samples. Both leukoplakia and GBC-OSCC had distinct methylation profiles as compared to normal oral tissue samples. Aberrant DNA methylation increases during the different stages of oral carcinogenesis, from premalignant lesions to carcinoma. We identified 846 and 5111 differentially methylated promoters in leukoplakia and GBC-OSCC, respectively, with a sizable fraction shared between the two sets. Further, we identified potential biomarkers from integrative analysis in gingivobuccal complex cancers and validated them in an independent cohort. Integration of genome, epigenome, and transcriptome data revealed candidate genes with gene expression synergistically regulated by copy number and DNA methylation changes. Regularised Cox regression identified 32 genes associated with patient survival. In an independent set of samples, we validated eight genes (FAT1, GLDC, HOXB13, CST7, CYB5A, MLLT11, GHR, LY75) from the integrative analysis and 30 genes from previously published reports. Bisulfite pyrosequencing validated GLDC (P = 0.036), HOXB13 (P < 0.0001) promoter hypermethylation, and FAT1 (P < 0.0001) hypomethylation in GBC-OSCC compared to normal controls. Conclusions Our findings identified methylation signatures associated with leukoplakia and gingivobuccal complex cancers. The integrative analysis in GBC-OSCC identified putative biomarkers that enhance existing knowledge of oral carcinogenesis and may potentially help in risk stratification and prognosis of GBC-OSCC. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Genome-wide DNA methylation profiling of HPV-negative leukoplakia and gingivobuccal complex cancers

et al. 2023

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“…Similarly, RALA upregulation is a marker of poor prognosis in BC patients [ 28 ]. Notably, our analysis suggested that proteasome-related pathways may be affected by IFNγ signaling, implying that: 1) some proteasome inhibitors could be tested as pharmacological tools for different cancer types, including BC [ 29 , 30 ]; 2) proteasome subunit (as PSMD8 ) deregulation can result in cancer progression, and resistance to proteasome inhibitors [ 31 , 32 ]; 3) IFNγ increases ISGylation, a protein modification associated with protein stability by competing with the ubiquitination pathway in BC [ [33] , [34] , [35] ]; and 4) the IFNγ repression of proteolysis-associated genes may be helpful in the development of novel strategies to treat this pathology.…”

Section: Discussionmentioning

confidence: 99%

Identification of genes modulated by interferon gamma in breast cancer cells

Tecalco-Cruz

Macı́as-Silva

Ramírez-Jarquín

et al. 2021

Biochemistry and Biophysics Reports

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Interferon gamma (IFNγ) plays a context-dependent dual tumor-suppressor and pro-tumorigenic roles in cancer. IFNγ induces morphological changes in breast cancer (BC) cells with or without estrogen receptor alpha (ERα) expression. However, IFNγ-regulated genes in BC cells remain unexplored. Here, we performed a cDNA microarray analysis of MCF-7 (ERα+) and MDA-MB-231 (HER2-/PR-/ERα-) cells with and without IFNγ treatment. We identified specific IFNγ−modulated genes in each cell type, and a small group of genes regulated by IFNγ common in both cell types. IFNγ treatment for an extended time mainly repressed gene expression shared by both cell types. Nonetheless, some of these IFNγ-repressed genes were seemingly deregulated in human mammary tumor samples, along with decreased IFNGR1 (an IFNγ receptor) expression. Thus, IFNγ signaling-elicited anti-tumor activities may be mediated by the downregulation of main IFNγ target genes in BC; however, it may be deregulated by the tumor microenvironment in a tumor stage-dependent manner.

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“…Current studies have shown that ISG15 could promote or inhibit cancer progression in different cancers; for example, free ISG15 can regulate immunity and promote NK cell infiltration, thus promoting breast cancer growth. Furthermore, mammary tumors had higher levels of ISG15 mRNA and protein than normal mammary tissue, and ISG15 may regulate cytoskeleton reorganization [ 33 , 34 , 35 ]. In pancreatic cancer, free ISG15 may be implicated in maintaining the stemness of tumor cells by increasing the phosphorylation level of ERK1/2 [ 36 ].…”

Section: Free Isg15 In Cancermentioning

confidence: 99%

The Functional Roles of ISG15/ISGylation in Cancer

Yuan

Qin

et al. 2023

Molecules

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The protein ISG15 encoded by interferon-stimulated gene (ISG) 15 is the first identified member of the ubiquitin-like protein family and exists in the form of monomers and conjugated complexes. Like ubiquitin, ISG15 can mediate an ubiquitin-like modification by covalently modifying other proteins, known as ISGylation. There is growing evidence showing that both the free and conjugated ISG15 are involved in multiple key cellular processes, including autophagy, exosome secretion, DNA repair, immune regulation, and cancer occurrence and progression. In this review, we aim to further clarify the function of ISG15 and ISGylation in cancer, demonstrate the important relationship between ISG15/ISGylation and cancer, and emphasize new insights into the different roles of ISG15/ISGylation in cancer progression. This review may contribute to therapeutic intervention in cancer. However, due to the limitations of current research, the regulation of ISG15/ISGylation on cancer progression is not completely clear, thus further comprehensive and sufficient correlation studies are still needed.

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Regulation and action of interferon-stimulated gene 15 in breast cancer cells

Cited by 5 publications

References 61 publications

Genome-wide DNA methylation profiling of HPV-negative leukoplakia and gingivobuccal complex cancers

Genome-wide DNA methylation profiling of HPV-negative leukoplakia and gingivobuccal complex cancers

Identification of genes modulated by interferon gamma in breast cancer cells

The Functional Roles of ISG15/ISGylation in Cancer

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