Rac1b enhances cell survival through activation of the JNK2/c-JUN/Cyclin-D1 and AKT2/MCL1 pathways.
Rac1b enhances cell survival through activation of the JNK2/c-JUN/Cyclin-D1 and AKT2/MCL1 pathways.
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Rac1b 通过激活 JNK2/c-JUN/Cyclin-D1 和 AKT2/MCL1 途径增强细胞存活
DOI：
10.18632/oncotarget.7602
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发表时间：
2016-04-05
期刊：
影响因子：
--
通讯作者：
Wang YP
中科院分区：
文献类型：
--
作者：
Li G;Ying L;Wang H;Wei SS;Chen J;Chen YH;Xu WP;Jie QQ;Zhou Q;Li YG;Wei YD;Wang YP
Rac1b 是小 GTP 酶 Rac1 的组成型激活、选择性剪接形式。先前的研究表明，Rac1b 可促进细胞增殖并抑制细胞凋亡。在本研究中，我们使用微阵列分析来检测稳定过表达Rac1b的HEK293T细胞和SW480人结肠癌细胞中差异表达的基因。我们发现促增殖基因 JNK2、c-JUN 和 cyclin-D1 以及抗凋亡基因 AKT2 和 MCL1 在这两个品系中均上调。 Rac1b 分别通过激活 JNK2/c-JUN/cyclin-D1 和 AKT2/MCL1 通路促进细胞增殖并抑制细胞凋亡。在野生型 Sprague-Dawley 大鼠的结肠上皮中检测到极低的 Rac1b 水平。敲除大鼠 Rac1 基因外显子 3b 或敲除 HT29 人结肠癌细胞中的内源性 Rac1b，仅下调 AKT2/MCL1 通路。我们的研究表明，极低水平的内源性 Rac1b 抑制细胞凋亡，而 Rac1b 上调既促进细胞增殖又抑制细胞凋亡。 AKT2/MCL1 通路可能对 Rac1b 调节更敏感。
Rac1b is a constitutively activated, alternatively spliced form of the small GTPase Rac1. Previous studies showed that Rac1b promotes cell proliferation and inhibits apoptosis. In the present study, we used microarray analysis to detect genes differentially expressed in HEK293T cells and SW480 human colon cancer cells stably overexpressing Rac1b. We found that the pro-proliferation genes JNK2, c-JUN and cyclin-D1 as well as anti-apoptotic AKT2 and MCL1 were all upregulated in both lines. Rac1b promoted cell proliferation and inhibited apoptosis by activating the JNK2/c-JUN/cyclin-D1 and AKT2/MCL1 pathways, respectively. Very low Rac1b levels were detected in the colonic epithelium of wild-type Sprague-Dawley rats. Knockout of the rat Rac1 gene exon-3b or knockdown of endogenous Rac1b in HT29 human colon cancer cells downregulated only the AKT2/MCL1 pathway. Our study revealed that very low levels of endogenous Rac1b inhibit apoptosis, while Rac1b upregulation both promotes cell proliferation and inhibits apoptosis. It is likely the AKT2/MCL1 pathway is more sensitive to Rac1b regulation.