Downregulation of TNFAIP2 suppresses proliferation and metastasis in esophageal squamous cell carcinoma through activation of the Wnt/β-catenin signaling pathway
Downregulation of TNFAIP2 suppresses proliferation and metastasis in esophageal squamous cell carcinoma through activation of the Wnt/β-catenin signaling pathway
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DOI：
10.3892/or.2017.5557
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发表时间：
2017-05-01
期刊：
影响因子：
4.2
通讯作者：
Wang, Bin
中科院分区：
文献类型：
--
作者：
Xie, Yunbo;Wang, Bin
肿瘤坏死因子-α（TNF-α）在肿瘤微环境中的恶性肿瘤形成中起关键作用。为了研究TNF-α在食管鳞状细胞癌（ESCC）中的作用，我们评估了下游基因TNF-α诱导蛋白2（TNFAIP 2）的表达谱，这是以前未知的ESCC。分别采用qRT-PCR和免疫组化方法检测24例新鲜和55例石蜡包埋标本中TNFAIP 2 mRNA和蛋白的表达水平。结果表明，TNFAIP 2 mRNA和蛋白水平在肿瘤细胞中过表达，TNFAIP 2过表达与T分期（p=0.049）、N分期（p=0.019）和国际抗癌联合会（UICC）分期（p=0.028）显著相关。在体外，TNFAIP 2在TNF α刺激的Eca 109、Kyse 150、Kyse 510和TE-10细胞中高度表达。慢病毒介导的TNFAIP 2的RNA干扰抑制细胞增殖、集落形成、迁移、侵袭和细胞周期。此外，发现LV-RNAi介导的TNFAIP 2通过降低β-连环蛋白下游的一些基因的表达来调节Wnt/β-连环蛋白（即，C-myc、细胞周期蛋白D1、MMP-7和Snail），并上调E-cadherin和p-GSK-3 β的表达。这些结果表明TNFAIP 2可能是食管鳞癌中一个潜在的致瘤基因。我们的数据表明TNFAIP 2过表达可能通过激活Wnt/β-连环蛋白信号通路促进ESCC的增殖和转移。
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 TNF alpha-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-3 beta. 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.