ISL1, a novel regulator of CCNB1, CCNB2 and c-MYC genes, promotes gastric cancer cell proliferation and tumor growth.
ISL1, a novel regulator of CCNB1, CCNB2 and c-MYC genes, promotes gastric cancer cell proliferation and tumor growth.
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ISL1是CCNB1、CCNB2和c-MYC基因的新型调节因子，促进胃癌细胞增殖和肿瘤生长
DOI：
10.18632/oncotarget.9269
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发表时间：
2016-06-14
期刊：
影响因子：
--
通讯作者：
Zhou C
中科院分区：
文献类型：
--
作者：
Shi Q;Wang W;Jia Z;Chen P;Ma K;Zhou C
Islet-1（ISL 1）属于LIM同源域转录因子家族，其仅在某些组织类型中特异性表达。以前，我们报道了ISL 1在胃癌（GC）中异常过表达。然而，它在GC中的作用尚不清楚。在这里，我们报告说，ISL 1是异常上调不仅在人胃癌组织中，而且在一些GC细胞系。在裸鼠中，上调的ISL 1表达增强了异种移植胃癌的发展，而ISL 1敲低抑制了GC的生长。ISL 1过表达促进GC细胞增殖、集落形成和软琼脂中的细胞生长，并促进GC细胞的细胞周期转换，表现出G2/M和S期细胞比例增加，G1期细胞比例减少。此外，我们提供的证据表明，ISL 1是一个新的调节细胞周期蛋白B1（CCNB 1），细胞周期蛋白B2（CCNB 2）和c-myc（c-MYC）基因。ISL 1通过与这些基因的启动子或增强子上的保守结合位点结合来激活这些基因在GC细胞中的表达。响应于ISL 1敲低，基因的表达水平降低。因此，ISL 1可能成为胃癌治疗的潜在靶点。
Islet-1 (ISL1) belongs to the LIM homeodomain transcription factor family, which is specifically expressed in certain tissue types only. Previously, we reported that ISL1 is aberrantly overexpressed in gastric cancer (GC). However, its role in GC is not clear. Here, we report that ISL1 is aberrantly upregulated not only in human gastric carcinoma tissues but also in some GC cell lines. Upregulated ISL1 expression enhanced xenografted gastric carcinoma development, while ISL1 knockdown inhibited GC growth in nude mice. ISL1 overexpression promoted GC cell proliferation, colony formation, and cell growth in soft agar, and facilitated cell cycle transition in GC cells, demonstrated an increase in the proportion of cells in the G2/M and S phases and a decrease in the proportion of cells in the G1 phase. Furthermore, we provide evidence that ISL1 is a novel regulator of the cyclin B1 (CCNB1), cyclin B2 (CCNB2) and c-myc (c-MYC) genes. ISL1 activated the expression of these genes in GC cells by binding to the conserved binding sites on their promoters or enhancers. The expression levels of the genes were decreased in response to ISL1 knockdown. Therefore, ISL1 may serve as a potential therapeutic target in GC.
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影响因子：
4.5
作者：
Han S;Kim HY;Park K;Cho HJ;Lee MS;Kim HJ;Kim YD
通讯作者：
Kim YD
影响因子：
3.5
作者：
Grabsch, H;Lickvers, K;Mueller, W
通讯作者：
Mueller, W
影响因子：
64.8
作者：
KARLSSON, O;THOR, S;EDLUND, T
通讯作者：
EDLUND, T
影响因子：
--
作者：
DONG, JL;ASA, SL;DRUCKER, DJ
通讯作者：
DRUCKER, DJ
ISL-1 的异常高表达代表胃癌的潜在预后因素。
影响因子：
3.3
作者：
Guo, Chen;Wang, Weiping;Zhou, Chunyan
通讯作者：
Zhou, Chunyan