PMID- 28393234 OWN - NLM STAT- MEDLINE DCOM- 20170627 LR - 20220317 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 37 IP - 5 DP - 2017 May TI - Downregulation of TNFAIP2 suppresses proliferation and metastasis in esophageal squamous cell carcinoma through activation of the Wnt/beta-catenin signaling pathway. PG - 2920-2928 LID - 10.3892/or.2017.5557 [doi] AB - Tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role in malignant tumor formation in the tumor microenvironment. To investigate the role of TNF-alpha in esophageal squamous cell carcinoma (ESCC), we assessed expression profiles of the downstream gene TNF-alpha-induced protein 2 (TNFAIP2), which e previously unknown in ESCC. TNFAIP2 mRNA and protein expression levels were examined by qRT-PCR and immunohistochemical analysis in 24 fresh and 55 paraffin‑embedded specimens, respectively. The results demonstrated that TNFAIP2 mRNA and protein levels were overexpressed in tumor cells, and TNFAIP2 overexpression was significantly associated with T stage (p=0.049), N stage (p=0.019) and the International Union Against Cancer (UICC) stage (p=0.028). In vitro, TNFAIP2 was highly expressed in TNFalpha-stimulated Eca109, Kyse150, Kyse510 and TE-10 cells. Lentivirus-mediated RNA interference of TNFAIP2 inhibited cell proliferation, colony formation, migration, invasion and the cell cycle. Moreover, LV-RNAi-mediated TNFAIP2 was found to regulate the Wnt/beta-catenin by decreasing expression of some genes downstream from beta-catenin (i.e., C-myc, cyclin D1, MMP-7 and Snail), and upregulating expression of E-cadherin and p-GSK-3beta. Taken together, these results show that TNFAIP2 may be a potential tumorigenesis gene in ESCC. Our data indicate that TNFAIP2 overexpression may facilitate proliferation and metastasis via activation of the Wnt/beta-catenin signaling pathway in ESCC. FAU - Xie, Yunbo AU - Xie Y AD - Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China. FAU - Wang, Bin AU - Wang B AD - Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China. LA - eng PT - Journal Article DEP - 20170405 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (Cytokines) RN - 0 (TNFAIP2 protein, human) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Carcinoma, Squamous Cell/genetics/*metabolism/*pathology MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - Cytokines/*genetics/*metabolism MH - Down-Regulation MH - Esophageal Neoplasms/genetics/*metabolism/*pathology MH - Esophageal Squamous Cell Carcinoma MH - Female MH - Humans MH - Male MH - Neoplasm Grading MH - Neoplasm Metastasis MH - Tumor Necrosis Factor-alpha/*metabolism MH - Wnt Signaling Pathway EDAT- 2017/04/11 06:00 MHDA- 2017/06/28 06:00 CRDT- 2017/04/11 06:00 PHST- 2016/08/10 00:00 [received] PHST- 2016/09/20 00:00 [accepted] PHST- 2017/04/11 06:00 [pubmed] PHST- 2017/06/28 06:00 [medline] PHST- 2017/04/11 06:00 [entrez] AID - 10.3892/or.2017.5557 [doi] PST - ppublish SO - Oncol Rep. 2017 May;37(5):2920-2928. doi: 10.3892/or.2017.5557. Epub 2017 Apr 5.