Current research status of TNFAIP8 in tumours and other inflammatory conditions (Review)

Hua, Jianyu; Zhuang, Guohong; Qi, Zhongquan

doi:10.3892/ijo.2021.5226

Cited by 9 publications

(7 citation statements)

References 70 publications

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“…Our findings are consistent with previous studies that have identified SOWAHD and TNFAIP8 as potential prognostic biomarkers in several different types of cancer 31,32 . For example, SOWAHD was found to be significantly downregulated in hepatocellular carcinoma, and its overexpression inhibited the proliferation and invasion of hepatocellular carcinoma cells.…”

Section: Discussionsupporting

confidence: 93%

Identification of neutrophil‐related genes and development of a prognostic model for cholangiocarcinoma

Xiong

Wang

et al. 2023

The Journal of Gene Medicine

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BackgroundCholangiocarcinoma is a prevalent gastrointestinal tumor with limited effective early diagnostic methods. The role of neutrophils in the context of cholangiocarcinoma remains largely unexplored.MethodsA comprehensive analysis was performed on a cohort of cholangiocarcinoma samples (TCGA‐CHOL) from the TCGA database to investigate the relationship between cholangiocarcinoma and neutrophils. Methodologies included single‐sample gene set enrichment analysis (ssGSEA), differential expression analysis, weighted gene co‐expression network analysis (WGCNA) and gene set enrichment analysis (GSEA).ResultsThe study identified a significant decrease of neutrophils in cholangiocarcinoma via ssGSEA. WGCNA and differential expression analysis led to the identification of a neutrophil‐related gene module comprised of 1059 genes. Cluster 1, showing a higher proportion of neutrophils, was linked to better survival outcomes. GSEA disclosed downregulation of complement, inflammatory response and interferon response pathways in Cluster 2, hinting at possible cholangiocarcinoma development triggers. A notable upregulation of PD1, PD‐L1 and CTLA4 was observed in Cluster 1, suggesting potential benefits from immunotherapy. A prognostic model was developed based on clinical data and expression levels of three prognostic genes (SOWAHD, TNFAIP8 and EBF3) showing satisfactory discrimination, calibration and clinical benefits. An overexpression of TNFAIP8 in cholangiocarcinoma cells was found, with its knockdown significantly inhibiting cell proliferation and migration.ConclusionsThis study elucidates a neutrophil‐related gene module and prognostic genes, offering insights into the role of neutrophils in cholangiocarcinoma development and progression. It also introduces a clinical prediction model for enhanced prognosis assessment. These findings may lay the groundwork for the development of innovative therapeutic strategies in cholangiocarcinoma treatment.

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Section: Discussionsupporting

confidence: 93%

Identification of neutrophil‐related genes and development of a prognostic model for cholangiocarcinoma

Xiong

Wang

et al. 2023

The Journal of Gene Medicine

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“…TNFAIP8 promoted GBM migration, invasion and proliferation, implying a transition towards MES subtype. Moreover, other researches have illustrated that TNFAIP8 exerts pro-angiogenic, anti-radiotherapy and immune suppressive effects in tumors (11,27). Considering that malignant behavior such as resistance to therapy, angiogenesis, increased motility and viability or recruitment of immune suppressive cells were hallmarks for MES GBM (31,32), it is reasonable to propose that TNFAIP8 exerted oncogenic effects through induction of MES phenotype in GBM.…”

Section: Discussionmentioning

confidence: 98%

“…TNFAIP8 plays a pivotal role in regulation of a variety of tumors and in ammatory diseases (27). Kumar et al rst identi ed a partial cDNA clone for TNFAIP8 which ampli ed in a metastatic and radioresistant head and neck squamous cell carcinoma (HNSCC)-derived cell line(8), endorsing its importance in cell survival, tumor growth and progression.…”

Section: Discussionmentioning

confidence: 99%

TNFAIP8 in Mesenchymal Glioblastoma Correlates with Metabolic Dysfunction and Poor Prognosis

Zhang

et al. 2022

Preprint

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TNFAIP8, a cytosolic TNF-α-inducible oncogenic molecule, plays pivotal roles in many types of cancers. However, the effect of TNFAIP8 on glioma remains elusive. In this study, we confirmed that TNFAIP8 promoted glioma viability and motility through alteration of nucleotide metabolism and tricarboxylic acid (TCA) cycle. Firstly, bioinformatic analysis indicated that TNFAIP8 expression elevated along with the WHO grade and predicted adverse prognosis in gliomas. Moreover, TNFAIP8 was enriched in gliomas with progressive genotypes, serving as an efficient indicator for mesenchymal glioma. To determine its function in glioblastoma progression, cell viability, migration and invasion were examined by loss/gain of function experiments. TNFAIP8 promoted glioma proliferation, migration, invasion and transition to mesenchymal phenotype. These findings were further confirmed in vivo. RNA sequencing and liquid chromatography-mass spectrometry (LC-MS) results showed impaired nucleotide metabolism and TCA cycle after TNFAIP8 knockdown, implying that TNFAIP8 enhanced glioblastoma progression via metabolic dysfunction. In summary, this study identified a novel oncogene in glioma with great potential for prognostic prediction and subtype identification. Alterations in metabolic process and transition towards mesenchymal subtype were supposed to be the underlying mechanisms for the oncogenic function of TNFAIP8.

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“…Target gene prediction and Dual-Luciferase reporter assay miR-24-1-5p's potential molecular targets were predicted using the miRDB database (https://mirdb.org/). Among the potential targets, we speci cally focused on TNFAIP8, which is an integral component of the TNFAIP8/NF-κB/TNF-α pathway known for its signi cant involvement in in ammatory diseases [13]. A conventional method was used to construct wild-type (WT)-TNFAIP8 plasmids fused with luciferase genes and mutant (MUT) TNFAIP8 fusion genes.…”

Section: Thp-1 Treatment With Pd-exosmentioning

confidence: 99%

Anti-inflammatory effects of Placenta-derived exosomal miR-24-1-5p through targeting TNFAIP8 and its implication in enhancing placental endotoxin tolerance in a model of lipopolysaccharide (LPS)-induced placental inflammation

Zhang

Chen

et al. 2023

Preprint

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Objective and design: Intra-amniotic infection (IAI) represents a potentially catastrophic complication during parturition, with potential for significant maternal and neonatal consequences. As a crucial immunological organ at the maternal-fetal interface, the immunoregulatory capacities of the placenta and the underlying molecular dynamics at play in the pathogenesis of IAI continue to be unclear. Recent studies have found that placenta-derived exosomes (Pd-Exos) and their contained microRNAs (miRNAs) may be involved in immune regulation during pregnancy. This study aimed to investigate the immunoregulatory function of the placenta in connection with the progression of IAI, as well as to elucidate its potential molecular mechanisms. Material or subjects: An IAI model was developed by co-culturing full-term placental explants obtained from elective cesarean sections with lipopolysaccharide (LPS). Using RT-qPCR and ELISA, the dynamic expression patterns of inflammatory factors within the placental explants were identified at varying time points post-LPS exposure. Pd-Exos were then isolated from the culture supernatant of placental explants and subjected to miRNA sequencing to pinpoint exosomal miRNAs integral to the immunoregulatory functions of the placenta. Subsequently, the role of a differentially expressed exosomal miRNA was validated. Results In the early phase of LPS stimulation, extensive pro-inflammatory responses were observed in placental explants, evidenced by the augmented expression of TNF-α and IL-1β. However, as the LPS stimulation progressed to the latter stages, a decrease in the pro-inflammatory response was noted, alongside a gradually surging anti-inflammatory response, signified by a diminishing ratio between pro-inflammatory and anti-inflammatory indicators (TNF-α/IL-10 and IL-1β/IL-1Ra). Following prolonged LPS stimulation of placental explants, the expression of miR-24-1-5p was upregulated in Pd-Exos. Upon internalization by receptor cells (THP-1 cells and Swan 71 cells), miR-24-1-5p can inhibit the expression of its target gene Tumor necrosis factor alpha-induced protein 8 (TNFAIP8), thereby suppressing the expression of downstream inflammatory factors TNF-α and IL-1β. Conclusion Prolonged exposure to the LPS in human term placental tissues induced endotoxin tolerance. Additionally, the placenta-derived exosomal miR-24-1-5p down-regulated the expression of the inflammatory markers TNF-α and IL-1β by inhibiting the functionality of TNFAIP8, thereby contributing to the placental endotoxin tolerance.

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Current research status of TNFAIP8 in tumours and other inflammatory conditions (Review)

Cited by 9 publications

References 70 publications

Identification of neutrophil‐related genes and development of a prognostic model for cholangiocarcinoma

Identification of neutrophil‐related genes and development of a prognostic model for cholangiocarcinoma

TNFAIP8 in Mesenchymal Glioblastoma Correlates with Metabolic Dysfunction and Poor Prognosis

Anti-inflammatory effects of Placenta-derived exosomal miR-24-1-5p through targeting TNFAIP8 and its implication in enhancing placental endotoxin tolerance in a model of lipopolysaccharide (LPS)-induced placental inflammation

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