TNPO2 operates downstream of DYNC1I1 and promotes gastric cancer cell proliferation and inhibits apoptosis

TNPO2 operates downstream of DYNC1I1 and promotes gastric cancer cell proliferation and inhibits apoptosis
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TNPO2在DYNC1I1下游发挥作用,促进胃癌细胞增殖并抑制细胞凋亡

DOI:
10.1002/cam4.2582
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发表时间:
2019-12-01
期刊:
影响因子:
4
通讯作者:
Qu, Xiujuan
Qu, Xiujuan
中科院分区:
医学3区
文献类型:
--
作者:
Gong, Libao;Wen, Ti;Qu, Xiujuan

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蛋白质进入细胞核在肿瘤的发展中起着重要作用。除了经典的核输入蛋白importin-beta和importin-alpha外,还有许多非经典的核输入蛋白,包括TNPO 2。TNPO 2作为一种非经典的核输入蛋白在肿瘤中的作用是有限的。我们前期的研究表明DYNC 1 I1是胃癌的一个不良预后因子,并能促进胃癌细胞的增殖和转移。表达谱芯片显示TNPO 2是其潜在的下游基因。DYNC 1 I1通过上调SP 1上调TNPO 2的表达,随后,SP 1募集并结合到P300-乙酰化TNPO 2启动子区域的组蛋白,从而促进TNPO 2的表达。同时,TNPO 2促进胃癌细胞增殖和抑制凋亡的机制可能依赖于P21的功能表达。
The import of proteins into the nucleus plays an important role in tumor development. In addition to the classical nuclear import proteins importin-beta and importin-alpha, there are many nonclassical nuclear import proteins that include TNPO2. The role of TNPO2 as a nonclassical nuclear import protein in tumors is limited. Our previous studies have shown that DYNC1I1 is a poor prognostic factor for gastric cancer and can promote the proliferation and metastasis of gastric cancer cells. An expression profile chip showed that TNPO2 was its potential downstream. DYNC1I1 upregulated TNPO2 expression by upregulating SP1, following which, SP1 recruited and bound to the P300-acetylated TNPO2 promoter region histones, and thus promoted TNPO2 expression. At the same time, TNPO2 promoted gastric cancer cell proliferation and inhibited apoptosis by a mechanism that might be depending on the functional expression of P21.