Cold-inducible RNA-binding protein, CIRP, inhibits DNA damage-induced apoptosis by regulating p53
Cold-inducible RNA-binding protein, CIRP, inhibits DNA damage-induced apoptosis by regulating p53
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DOI：
10.1016/j.bbrc.2015.07.066
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发表时间：
2015-08-28
影响因子：
3.1
通讯作者：
Jang, Ho Hee
中科院分区：
文献类型：
--
作者：
Lee, Hae Na;Ahn, Sung-Min;Jang, Ho Hee
CIRP与细胞凋亡有关，但其作用机制仍不清楚。为了确定CIRP在DNA损伤诱导的细胞凋亡中的作用，我们进行了CIRP过表达和敲低实验，以研究CIRP对细胞凋亡途径中关键分子的影响。足叶乙甙处理诱导DNA损伤诱导的细胞凋亡。我们发现，CIRP敲低增加p53水平，这反过来又上调促凋亡基因和下调抗凋亡基因。与此相反，CIRP过表达降低p53水平，这反过来下调促凋亡基因和上调抗凋亡基因。促凋亡基因和抗凋亡基因表达水平的变化改变了细胞生与死之间的平衡。CIRP表达被慢性炎症上调，并且这种现象在由慢性炎症引起的癌症中提供了有趣的干预机会。慢性炎症上调CIRP，CIRP反过来抑制细胞凋亡。因此，抑制上调的CIRP的功能可能在癌症中具有治疗价值。(C)2015 Elsevier Inc. All rights reserved.
CIRP has been implicated in apoptosis, yet its mechanism of action remains unknown. To determine the role of CIRP in DNA damage-induced apoptosis, we performed CIRP overexpression and knockdown experiments to investigate the effects of CIRP on key molecules in apoptosis pathway. Etoposide treatment was used to induce DNA damage-induced apoptosis. We found that CIRP knockdown increased p53 level, which in turn up-regulated pro-apoptotic genes and down-regulated anti-apoptotic genes. In contrast, CIRP overexpression decreased p53 level, which in turn down-regulated pro-apoptotic genes and up-regulated anti-apoptotic genes. The change in the expression levels of pro-apoptotic and antiapoptotic genes shifts the balance between life and death of cells. CIRP expression is upregulated by chronic inflammation, and this phenomenon provides an interesting interventional opportunity in cancers arising from chronic inflammation. Chronic inflammation up-regulates CIRP which in turn inhibit apoptosis. Therefore, inhibiting the function of up-regulated CIRP may have a therapeutic value in cancer. (C) 2015 Elsevier Inc. All rights reserved.