NUB1 and FAT10 Proteins as Potential Novel Biomarkers in Cancer: A Translational Perspective

Arshad, Maria; Hamid, Nazefah Abdul; Chan, Mun Chiang; Ismail, Fuad; Tan, Geok Chin; Tan, Ka-Liong

doi:10.3390/cells10092176

Cited by 6 publications

(3 citation statements)

References 72 publications

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“…Ubiquitin-like modifier-activating enzyme 6 (UBA6), which activates ubiquitin and uses ubiquitin-conjugating enzyme (E2) to target proteins to proteasomal degradation, was also aligned [ 30 ]. UBA6 activates human leukocyte antigen F-adjacent transcript 10 (FAT10), which serves as 26S proteasome-targeting signal, to be involved in epithelial-mesenchymal transition (EMT), invasion, and apoptosis in hepatocellular carcinoma [ 31 ]. Dysregulation of a protein ubiquitination cascade is implicated in various human diseases, including neurodegenerative disorders and cancer [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Short Linear Motifs Orchestrate Functioning of Human Proteins during Embryonic Development, Redox Regulation, and Cancer

et al. 2022

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Short linear motifs (SLiMs) are evolutionarily conserved functional modules of proteins that represent amino acid stretches composed of 3 to 10 residues. The biological activities of two short peptide segments of human alpha-fetoprotein (AFP), a major embryo-specific and cancer-related protein, have been confirmed experimentally. This is a heptapeptide segment LDSYQCT in domain I designated as AFP14–20 and a nonapeptide segment EMTPVNPGV in domain III designated as GIP-9. In our work, we searched the UniprotKB database for human proteins that contain SLiMs with sequence similarity to the both segments of human AFP and undertook gene ontology (GO)-based functional categorization of retrieved proteins. Gene set enrichment analysis included GO terms for biological process, molecular function, metabolic pathway, KEGG pathway, and protein–protein interaction (PPI) categories. We identified the SLiMs of interest in a variety of non-homologous proteins involved in multiple cellular processes underlying embryonic development, cancer progression, and, unexpectedly, the regulation of redox homeostasis. These included transcription factors, cell adhesion proteins, ubiquitin-activating and conjugating enzymes, cell signaling proteins, and oxidoreductase enzymes. They function by regulating cell proliferation and differentiation, cell cycle, DNA replication/repair/recombination, metabolism, immune/inflammatory response, and apoptosis. In addition to the retrieved genes, new interacting genes were identified. Our data support the hypothesis that conserved SLiMs are incorporated into non-homologous proteins to serve as functional blocks for their orchestrated functioning.

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Section: Discussionmentioning

confidence: 99%

Short Linear Motifs Orchestrate Functioning of Human Proteins during Embryonic Development, Redox Regulation, and Cancer

et al. 2022

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“…Conversely, FAT10 limits type I INF production in order to avoid exceeding inflammation and tissue destruction [ 154 ]. Based on all these results, FAT10 was proposed as a new biomarker in cancer, including the HCC [ 155 , 156 ].…”

Section: Non-classical Hla Class I Molecules (Hla-ib)mentioning

confidence: 99%

Non-Classical HLA Class 1b and Hepatocellular Carcinoma

Tornesello

Racanelli

et al. 2023

Biomedicines

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A number of studies are underway to gain a better understanding of the role of immunity in the pathogenesis of hepatocellular carcinoma and to identify subgroups of individuals who may benefit the most from systemic therapy according to the etiology of their tumor. Human leukocyte antigens play a key role in antigen presentation to T cells. This is fundamental to the host’s defense against pathogens and tumor cells. In addition, HLA-specific interactions with innate lymphoid cell receptors, such those present on natural killer cells and innate lymphoid cell type 2, have been shown to be important activators of immune function in the context of several liver diseases. More recent studies have highlighted the key role of members of the non-classical HLA-Ib and the transcript adjacent to the HLA-F locus, FAT10, in hepatocarcinoma. The present review analyzes the major contribution of these molecules to hepatic viral infection and hepatocellular prognosis. Particular attention has been paid to the association of natural killer and Vδ2 T-cell activation, mediated by specific HLA class Ib molecules, with risk assessment and novel treatment strategies to improve immunotherapy in HCC.

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“…NEDD8 Ultimate Buster-1 (NUB1) is an interferon-inducible gene whose overexpression inhibits cell growth. It is known to play an important role in cancer and cell physiology (18)(19)(20), but its role in sepsis is not clear.…”

Section: B C Amentioning

confidence: 99%

Identification of biomarkers related to sepsis diagnosis based on bioinformatics and machine learning and experimental verification

Wang

Zhang

et al. 2023

Front. Immunol.

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Sepsis is a systemic inflammatory response syndrome caused by bacteria and other pathogenic microorganisms. Every year, approximately 31.5 million patients are diagnosed with sepsis, and approximately 5.3 million patients succumb to the disease. In this study, we identified biomarkers for diagnosing sepsis analyzed the relationships between genes and Immune cells that were differentially expressed in specimens from patients with sepsis compared to normal controls. Finally, We verified its effectiveness through animal experiments. Specifically, we analyzed datasets from four microarrays(GSE11755、GSE12624、GSE28750、GSE48080) that included 106 blood specimens from patients with sepsis and 69 normal human blood samples. SVM-RFE analysis and LASSO regression model were carried out to screen possible markers. The composition of 22 immune cell components in patients with sepsis were also determined using CIBERSORT. The expression level of the biomarkers in Sepsis was examined by the use of qRT-PCR and Western Blot (WB). We identified 50 differentially expressed genes between the cohorts, including 2 significantly upregulated and 48 significantly downregulated genes, and KEGG pathway analysis identified Salmonella infection, human T cell leukemia virus 1 infection, Epstein−Barr virus infection, hepatitis B, lysosome and other pathways that were significantly enriched in blood from patients with sepsis. Ultimately, we identified COMMD9, CSF3R, and NUB1 as genes that could potentially be used as biomarkers to predict sepsis, which we confirmed by ROC analysis. Further, we identified a correlation between the expression of these three genes and immune infiltrate composition. Immune cell infiltration analysis revealed that COMMD9 was correlated with T cells regulatory (Tregs), T cells follicular helper, T cells CD8, et al. CSF3R was correlated with T cells regulatory (Tregs), T cells follicular helper, T cells CD8, et al. NUB1 was correlated with T cells regulatory (Tregs), T cells gamma delta, T cells follicular helper, et al. Taken together, our findings identify potential new diagnostic markers for sepsis that shed light on novel mechanisms of disease pathogenesis and, therefore, may offer opportunities for therapeutic intervention.

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NUB1 and FAT10 Proteins as Potential Novel Biomarkers in Cancer: A Translational Perspective

Cited by 6 publications

References 72 publications

Short Linear Motifs Orchestrate Functioning of Human Proteins during Embryonic Development, Redox Regulation, and Cancer

Short Linear Motifs Orchestrate Functioning of Human Proteins during Embryonic Development, Redox Regulation, and Cancer

Non-Classical HLA Class 1b and Hepatocellular Carcinoma

Identification of biomarkers related to sepsis diagnosis based on bioinformatics and machine learning and experimental verification

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