Regulation of PMP22 mRNA by G3BP1 affects cell proliferation in breast cancer cells.

Regulation of PMP22 mRNA by G3BP1 affects cell proliferation in breast cancer cells.
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DOI:
10.1186/1476-4598-12-156
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发表时间:
2013-12-09
期刊:
影响因子:
37.3
通讯作者:
Larsson C
Larsson C
中科院分区:
医学1区
文献类型:
--
作者:
Winslow S;Leandersson K;Larsson C

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mRNA的调节是控制蛋白质水平的一种方式,从而控制重要的细胞过程,如生长、侵袭和凋亡。G3 BPs构成了一个mRNA结合蛋白家族,在几种癌症类型中过表达,包括乳腺癌、结肠癌和胰腺癌。据报道,G3 BP可稳定和诱导特异性mRNA的降解。在这里,我们表明,G3 BP 1,而不是G3 BP 2,支持几种乳腺癌细胞系的增殖。G3 BP 1-和G3 BP 2-耗尽的细胞的全局基因表达分析表明,主要是G3 BP 1,和少得多的G3 BP 2,影响mRNA表达水平。外周髓磷脂蛋白22(PMP 22)是一个受G3 BP 1缺失显著影响的基因,其导致表达增加2-3倍。PMP 22的消耗导致增殖增加,并且在PMP 22消耗后未观察到G3 BP 1介导的对增殖的影响。这表明G3 BP 1在乳腺癌细胞中调节细胞增殖的新作用,可能通过对PMP 22表达的调节作用。
Regulation of mRNAs is one way to control protein levels and thereby important cellular processes such as growth, invasion and apoptosis. G3BPs constitute a family of mRNA-binding proteins, shown to be overexpressed in several cancer types, including breast, colon and pancreas cancer. G3BP has been reported to both stabilize and induce degradation of specific mRNAs. Here, we show that G3BP1, but not G3BP2, supports proliferation of several breast cancer cell lines. Global gene expression analyses of G3BP1- and G3BP2-depleted cells indicate that primarily G3BP1, and much less G3BP2, influences mRNA expression levels. Peripheral myelin protein 22 (PMP22) was one gene that was significantly influenced by G3BP1 depletion which led to a 2–3 fold increased expression. Depletion of PMP22 resulted in increased proliferation and the G3BP1-mediated effect on proliferation was not seen upon PMP22-depletion. This indicates a novel role for G3BP1 in the regulation of cell proliferation in breast cancer cells, perhaps via a regulatory effect on PMP22 expression.
新型周围神经系统髓磷脂蛋白的表征(PMP-22/SR13)。
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