Genetic polymorphisms in <i>TNIP1</i> increase the risk of gastric carcinoma

Zhao, Lei; Shi, Yuting; Na, Yuyan; Zhang, Qi; Cao, Sizhe; Duan, Xianglong; Zhang, Xiyang; Yang, Hua; Jin, Tianbo; Li, Yiming

doi:10.18632/oncotarget.9637

Cited by 8 publications

(10 citation statements)

References 25 publications

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“…21,22 TNIP1 and TNFα-induced NF-κB activity play key roles in immune diseases and inflammatory responses. 23 Genetic polymorphisms of TNIP1 are also reportedly correlated with elevated risk of gastric carcinoma or glioma prognosis 24,25 ; however, the detailed roles of TNIP1 in glioma still remain to be elucidated. Here, we report that high levels of TNIP1 show a positive correlation with glioma cell proliferation and poor survival in glioma patients.…”

Section: Introductionmentioning

confidence: 99%

TNIP1‐mediated TNF‐α/NF‐κB signalling cascade sustains glioma cell proliferation

Lei

et al. 2019

J Cellular Molecular Medi

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As a malignant tumour of the central nervous system, glioma exhibits high incidence and poor prognosis. Although TNIP1 and the TNF‐α/NF‐κB axis play key roles in immune diseases and inflammatory responses, their relationship and role in glioma remain unknown. Here, we revealed high levels of TNIP1 and TNF‐α/NF‐κB in glioma tissue. Glioma cell proliferation was activated with TNF‐α treatment and showed extreme sensitivity to the TNF receptor antagonist. Furthermore, loss of TNIP1 disbanded the A20 complex responsible for IκB degradation and NF‐κB nucleus translocation, and consequently erased TNFα‐induced glioma cell proliferation. Thus, our investigation uncovered a vital function of the TNIP1‐mediated TNF‐α/NF‐κB axis in glioma cell proliferation and provides novel insight into glioma pathology and diagnosis.

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Section: Introductionmentioning

confidence: 99%

TNIP1‐mediated TNF‐α/NF‐κB signalling cascade sustains glioma cell proliferation

Lei

et al. 2019

J Cellular Molecular Medi

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“…Multiple independent and race‐specific SLE risk haplotypes spanning the TNIP1 locus have been identified, including independent H1 and H2 haplotypes that we previously identified in European Americans . Genetic variability within the TNIP1 locus has also been associated with several other autoimmune diseases, including Sjögren's syndrome , systemic sclerosis , psoriatic arthritis , and psoriasis , as well as asthma and some cancers . TNIP1 encodes the polyubiquitin binding protein A20‐binding inhibitor of NF‐κB (ABIN‐1).…”

Section: Introductionmentioning

confidence: 96%

Role of Systemic Lupus Erythematosus Risk Variants With Opposing Functional Effects as a Driver of Hypomorphic Expression of TNIP1 and Other Genes Within a Three‐Dimensional Chromatin Network

Pasula

Tessneer

et al. 2020

Arthritis & Rheumatology

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Objective. Genetic variants in the region of tumor necrosis factor-induced protein 3-interacting protein 1 (TNIP1) are associated with autoimmune disease and reduced TNIP1 gene expression. The aim of this study was to define the functional genetic mechanisms driving TNIP1 hypomorphic expression imparted by the systemic lupus erythematosus-associated TNIP1 H1 risk haplotype.Methods. Dual luciferase expression and electrophoretic mobility shift assays were used to evaluate the allelic effects of 11 risk variants on enhancer function and nuclear protein binding in immune cell line models (Epstein-Barr virus [EBV]-transformed human B cells, Jurkat cells, and THP-1 cells), left in a resting state or stimulated with phorbol 12-myristate 13-acetate/ionomycin. HiChIP was used to define the regulatory 3-dimensional (3-D) chromatin network of the TNIP1 haplotype by detecting in situ long-range DNA contacts associated with H3K27ac-marked chromatin in EBV B cells. Then, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the expression of genes within the 3-D chromatin network.Results. Bioinformatics analyses of 50 single-nucleotide polymorphisms on the TNIP1 H1 risk haplotype identified 11 non-protein-coding variants with a high likelihood of influencing TNIP1 gene expression. Eight variants in EBV B cells, 5 in THP-1 cells, and 2 in Jurkat cells exhibited various allelic effects on enhancer activation, resulting in a cumulative suppressive effect on TNIP1 expression (net effect of risk variants −7.14 fold, −6.80 fold, and −2.44 fold, respectively; n > 3). Specifically, in EBV B cells, only 2 variants (rs10057690 and rs13180950) exhibited allele-specific loss of both enhancer activity and nuclear protein binding (each P < 0.01 relative to nonrisk alleles). In contrast, the rs10036748 risk allele reduced binding affinities of the transcriptional repressors basic helix-loop-helix family member 40/differentially expressed in chondrocytes 1 (bHLHe40/DEC1) (P < 0.05 relative to nonrisk alleles) and CREB-1 (P not significant) in EBV B cells, resulting in a gain of enhancer activity (P < 0.05). HiChIP and qRT-PCR analyses revealed that overall transcriptional repression of the TNIP1 haplotype extended to the neighboring genes DCTN4 and GMA2, both of which also showed decreased expression in the presence of the TNIP1 risk haplotype (P < 0.001 and P < 0.01, respectively, relative to the nonrisk haplotype); notably, it was found that these genes share a 3-D chromatin network.Conclusion. Hypomorphic TNIP1 expression results from the combined concordant and opposing effects of multiple risk variants carried on the TNIP1 risk haplotype, with the strongest regulatory effect in B lymphoid lineage cells. Furthermore, the TNIP1 risk haplotype effect extends to neighboring genes within a shared chromatin network.

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“…The gene for tumor necrosis factor‐α‐induced protein 3‐interacting protein 1 (TNIP1), which is located on chromosome 5q33 and also known as VAN , NAF1 , ABIN‐1 and nip40–1 , encodes an A20‐binding protein that plays an important role in autoimmunity, chronic inflammation and cancer by blocking the activation of nuclear factor‐kappa B (NF‐κB) . It has been reported that TNIP1 is associated with certain diseases, such as gastric carcinoma . Another study demonstrated that blocking the NF‐κB signaling pathway inhibited esophageal cancer proliferation and metastasis .…”

Section: Introductionmentioning

confidence: 99%

“…15 It has been reported that TNIP1 is associated with certain diseases, such as gastric carcinoma. 16 Another study demonstrated that blocking the NF-κB signaling pathway inhibited esophageal cancer proliferation and metastasis. 14 Thus, we investigated the effects of the TNIP1 gene on glioma prognosis.…”

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confidence: 99%