Decreased expression of interferon-induced protein 2 (IFIT2) by Wnt/β-catenin signaling confers anti-apoptotic properties to colorectal cancer cells.
Decreased expression of interferon-induced protein 2 (IFIT2) by Wnt/β-catenin signaling confers anti-apoptotic properties to colorectal cancer cells.
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DOI：
10.18632/oncotarget.22122
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发表时间：
2017-11-21
期刊：
影响因子：
--
通讯作者：
Furukawa Y
中科院分区：
文献类型：
--
作者：
Ohsugi T;Yamaguchi K;Zhu C;Ikenoue T;Furukawa Y
Wnt信号通路受损通过激活β-catenin/TCF7L2复合体在结直肠癌的发生发展中起重要作用。尽管Wnt/β-catenin信号上调的基因已被广泛研究，但下调基因的作用却知之甚少。在这项研究中，我们探索了β-catenin siRNA或显性阴性形式的TCF7L2(DnTCF7L2)转染的结直肠癌细胞的整体基因表达，并鉴定了一组受Wnt/β-catenin信号下调的基因。在这些基因中，我们重点介绍了IFIT2，这是一种编码干扰素诱导蛋白的基因，具有四肽重复序列。用含有该基因5‘侧翼区域的质粒进行的报告基因分析表明，该报告基因的活性可以通过转导β-catenin siRNA或dnTCF7L2来增强，这表明该区域作为β-catenin/TCF7L2复合体的下游参与了转录调控。与此结果一致的是，结直肠癌组织中IFIT2的表达显著低于正常组织。外源性IFIT2的表达降低了结直肠癌细胞的增殖，增加了细胞的凋亡率。提示Wnt/β-Catenin信号通路下调IFIT2的表达可能通过抑制细胞凋亡在结直肠癌的发生发展中起重要作用。
Impaired Wnt signaling pathway plays a crucial role in the development of colorectal cancer through activation of the β-catenin/TCF7L2 complex. Although genes up-regulated by Wnt/β-catenin signaling have been intensively studied, the roles of down-regulated genes are poorly understood. In this study, we explored a global gene expression of colorectal cancer cells transfected with β-catenin siRNAs or a dominant negative form of TCF7L2 (dnTCF7L2), and identified a set of genes down-regulated by Wnt/β-catenin signaling. Among the genes, we focused here on IFIT2, a gene encoding interferon-induced protein with tetratricopeptide repeats. A reporter assay using plasmids containing a 5’-flanking region of the gene showed that the reporter activity was enhanced by either transduction of β-catenin siRNA or dnTCF7L2, suggesting that the region is involved in the transcriptional regulation as a downstream of the β-catenin/TCF7L2 complex. Consistent with this result, expression of IFIT2 was significantly lower in colorectal cancer tissues than that in normal tissues. Exogenous IFIT2 expression decreased cell proliferation and increased apoptosis of colorectal cancer cells. These data suggested that the down-regulation of IFIT2 by Wnt/β-catenin signaling may play a vital role in human colorectal carcinogenesis through the suppression of apoptosis.
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影响因子：
5
作者：
Andersen, J.;VanScoy, S.;Reich, N. C.
通讯作者：
Reich, N. C.
影响因子：
64.8
作者：
Sansom, Owen J.;Meniel, Valerie S.;Clarke, Alan R.
通讯作者：
Clarke, Alan R.
DOI：
10.1073/pnas.83.23.8929
发表时间：
1986-12-01
影响因子：
11.1
作者：
LEVY, D;LARNER, A;DARNELL, JE
通讯作者：
DARNELL, JE
DOI：
10.1073/pnas.96.4.1603
发表时间：
1999-02-16
影响因子：
11.1
作者：
Mann, B;Gelos, M;Hanski, C
通讯作者：
Hanski, C
影响因子：
3.8
作者：
Feng X;Wang Y;Ma Z;Yang R;Liang S;Zhang M;Song S;Li S;Liu G;Fan D;Gao S
通讯作者：
Gao S