TNFAIP3 overexpression is an independent factor for poor survival in esophageal squamous cell carcinoma

Abstract

Tumor necrosis factor α induced protein 3 (TNFAIP3) is a protein that is induced by TNF-mediated NF-κB activation and has a dual function in regulating NF-κB. TNFAIP3 is associated with inflammatory carcinogenesis in many cancer types. However, the clinical significance of TNFAIP3 expression and function in esophageal squamous cell carcinoma (ESCC) has not yet been reported. We examined 149 ESCC tissue specimens to determine the clinical significance of TNFAIP3 by immunohistochemistry. Western blot analyses were used to detect TNFAIP3 expression in TE-1, TE-8, TE-15 and KYSE-70 ESCC cells and in Het-1A, a non-cancerous esophageal cell line. TNFAIP3 protein knockdown was conducted using small-interfering RNA to investigate its impact on cell proliferation, migration and invasion. Significant correlations between TNFAIP3 expression and differentiation (P=0.04) among clinicopathological characteristics of ESCC patients were demonstrated, and high TNFAIP3 expression was associated with poor survival (P=0.02). Moreover, multivariate analysis result showed that high TNFAIP3 expression was an independent factor for poor survival (P=0.04). In vitro analysis showed high expression of TNFAIP3 protein in TE-15 cells and low expression in Het-1A cells. Furthermore, the proliferation, migration and invasion of TE-15 cells after TNFAIP3 suppression by siRNA were significantly reduced. These findings suggest that TNFAIP3 protein may be an independent prognostic marker for poor survival, and a promising target for ESCC therapy.

Genome-wide analyses of long non-coding RNA expression profiles and functional network analysis in esophageal squamous cell carcinoma

“…The results of cis-regulation showed that the genes encoding TNFAIP3 and lnc-KIAA1244-2 are located at the same locus. It was previously reported that TNFAIP3 is involved in proliferation, migration and invasion of EC cells 29 . By knockdown assays, we demonstrated that lnc-KIAA1244-2 could promote cell proliferation and regulate TNFAIP3 expression.…”

The pleiotropic effects of TNFα in breast cancer subtypes is regulated by TNFAIP3/A20

“…Although emerging data in cancer supports the notion that A20 may mediate TNFα-induced aggressive properties in some cancer types (17, 18, 20, 22), its central role in immune system is to protect immune cells from TNFα-induced cytotoxicity (11, 12). nduced r A20 red the potential role of rts mmatory cyttionization of MDSCs in preclinical and clinical settings.…”

“…Relative A20 overexpression in glioblastoma stem cells (GSCs) compared to non-stem glioblastoma cells is shown to play a role in maintenance of self-renewing GSCs as well as protection from TNF-induced apoptosis (20). Furthermore, overexpression and prognostic utility of A20 in multiple solid tumors has also been reported (18, 20, 22). In line with these findings, a recent study demonstrated that elevated A20 levels in basal breast cancer subtypes promote the metastatic properties of this subtype by inducing an epithelial mesenchymal transition (EMT) phenotype via multi-monoubiquitylation of Snail1 (17).…”

The inhibitory effects of COL1A2 on colorectal cancer cell proliferation, migration, and invasion

“…TNFAIP3 is responsible for cytokine-mediated immune and inflammatory responses by inhibiting both NF-κB signaling and tumor necrosis factor-mediated apoptosis. The downregulation of TNFAIP3 is correlated with distant metastasis and poor patient prognosis in many types of cancer 37 , 38 . CCND1, a member of the cyclin family, is a regulatory component of CDK4 and CDK6.…”