The miR-184 Binding-Site rs8126 T&gt;C Polymorphism in TNFAIP2 Is Associated with Risk of Gastric Cancer

Xu, Yu; Ma, Hongxia; Yu, Hongping; Liu, Zhensheng; Wang, Li E.; Tan, Dongfeng; Muddasani, Ramya; Lu, Victoria; Ajani, Jaffer A.; Wang, Yanong; Wei, Qingyi

doi:10.1371/journal.pone.0064973

Cited by 33 publications

(37 citation statements)

References 29 publications

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“…Overexpression of TNFAIP1 or TNFAIP2 correlates with tumor invasion and metastasis, and serves as an independent prognostic indicator for breast cancer (9) and nasopharyngeal carcinoma (15). The TNFAIP2 miRNA binding site (s8126 T>C SNP) is also correlated with a significantly elevated risk of gastric cancer, suggesting a marker for susceptibility to gastric cancer (16). To verify the correlation of TNFAIP1 expression with OS, we examined the expression of TNFAIP1 in human OS tissues.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of TNFAIP1 inhibits growth and induces apoptosis in osteosarcoma cells through inhibition of the nuclear factor-κB pathway

et al. 2014

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Abstract. Tumor necrosis factor-α-inducible protein-1 (TNFAIP1) plays a role in DNA synthesis, DNA repair, cell apoptosis and human diseases including cancer, and may be involved in tumor progression and metastases. However, little is known concerning the function of TNFAIP1 in human osteosarcoma (OS). The aim of the present study was to investigate the function and underlying mechanisms of TNFAIP1 in human OS. The expression of TNFAIP1 was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was performed to explore the effects of lentiviral-mediated TNFAIP1 siRNA (siTNFAIP1) on cell proliferation, invasive potential and apoptosis by MTT and Transwell assays and flow cytometric analysis in OS (MG-63 and U-2 OS) cells. The results showed that the expression of TNFAIP1 protein was significantly increased in OS tissues compared with that in adjacent noncancerous tissues (ANCTs) (73.3 vs. 48.9%, P=0.018), and was correlated with the distant metastasis of the patients with OS (P=0.029). Knockdown of TNFAIP1 suppressed cell proliferation and invasion, and induced cell apoptosis in the OS cells together with the downregulation of p65 nuclear factor-κB (NF-κB), proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2 (MMP-2) and upregulation of caspase-3. Collectively, our findings indicate that high expression of TNFAIP1 is associated with distant metastasis of OS, and knockdown of TNFAIP1 inhibits the growth and invasion, and induces apoptosis in OS cells through inhibition of the NF-κB pathway, suggesting that TNFAIP1 may act as a potential therapeutic target for the treatment of cancer.

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Section: Discussionmentioning

confidence: 99%

Knockdown of TNFAIP1 inhibits growth and induces apoptosis in osteosarcoma cells through inhibition of the nuclear factor-κB pathway

et al. 2014

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“…These genes include TNFAIP2 [19], FGFR4 [20][21][22], CXCL10 [23], CEP55 [24], CXCL1 [25,26], LIMK1 [27], LAMC2 [28], APOE [29], INHBA [30], OSMR [31,32], APOC1 [33], KLF4 [34], MMP14 [35], ADH1C [36], COL6A3 [37,38], CCT2 [39], NOL8 [40], EPHB4 [41] and MCM2 [42,43]. Ye et al reported that high expression of FGFR4 protein is associated with a poor prognosis in patients with advanced GC and expedites the progress of advanced GC [20].…”

Section: Discussionmentioning

confidence: 99%

“…SNPs in miRNA binding sites could affect its binding affinity to target genes. A recent study showed that the TNFAIP2 miRNA binding site rs8126 T>C SNP may be a marker for susceptibility to GC [19].…”

Section: Discussionmentioning

confidence: 99%

A Novel Gene Expression-Based Prognostic Scoring System to Predict Survival in Gastric Cancer

Wang¹

2017

Gastroenterology

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Analysis of gene expression patterns in gastric cancer (GC) can help to identify a comprehensive panel of gene biomarkers for predicting clinical outcomes and to discover potential new therapeutic targets. Here, a multi-step bioinformatics analytic approach was developed to establish a novel prognostic scoring system for GC. We first identified 276 genes that were robustly differentially expressed between normal and GC tissues, of which, 249 were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. The biological functions of 249 genes are related to cell cycle, RNA/ncRNA process, acetylation and extracellular matrix organization. A network was generated for view of the gene expression architecture of 249 genes in 265 GCs. Finally, we applied a canonical discriminant analysis approach to identify a 53-gene signature and a prognostic scoring system was established based on a canonical discriminant function of 53 genes. The prognostic scores strongly predicted patients with GC to have either a poor or good OS. Our study raises the prospect that the practicality of GC patient prognosis can be assessed by this prognostic scoring system.

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“…Additionally, downregulating MiR-29c conferred a growth advantage on tumor cells via aberrant expression of RCC2 in gastric carcinoma cells [24]. Of note, the SNP (single nucleotide polymorphism) of TNFAIP2 (the key gene in apoptosis) in miRNA binding site, rs8126 T>C, caused high susceptibility to gastric cancer [25], which also indicate the role of miRNA as tumor suppressor. Together, miRNA can serve as oncogenes or tumor suppressors during tumorigenesis of gastric cancer and may be a potential gastric cancer therapeutic target.…”

Section: The Involvement Of Mirnas As Oncogenes or Tumor Suppressors mentioning

confidence: 99%

The Role of miRNAs in Gastric Cancer

Tang¹,

Tang²,

Xie³

2013

J Gastrointest Dig Syst

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Despite promising developments of treatment, the mortality of gastric cancer remains high. MicroRNAs (miRNAs) are non-coding RNA molecules. There are extensive evidences that miRNAs play a dual role, as oncogenes or tumor suppressors through regulating cell proliferation, differentiation, and apoptosis. Additionally, some miRNAs, as promising diagnostic and prognostic biomarkers, are specifically related to gastric cancer. In the current review, we have summarized recent data concerning miRNAs in patient with gastric cancer, allowing us a better understanding miRNA as the prognostic and diagnostic biomarkers and the new targets for clinical therapeutic interventions for gastric cancer.

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The miR-184 Binding-Site rs8126 T>C Polymorphism in TNFAIP2 Is Associated with Risk of Gastric Cancer

Cited by 33 publications

References 29 publications

Knockdown of TNFAIP1 inhibits growth and induces apoptosis in osteosarcoma cells through inhibition of the nuclear factor-κB pathway

Knockdown of TNFAIP1 inhibits growth and induces apoptosis in osteosarcoma cells through inhibition of the nuclear factor-κB pathway

A Novel Gene Expression-Based Prognostic Scoring System to Predict Survival in Gastric Cancer

The Role of miRNAs in Gastric Cancer

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