miR-200c regulates induction of apoptosis through CD95 by targeting FAP-1.
miR-200c regulates induction of apoptosis through CD95 by targeting FAP-1.
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DOI：
10.1016/j.molcel.2010.05.018
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发表时间：
2010-06-25
期刊：
影响因子：
16
通讯作者：
Peter ME
中科院分区：
文献类型：
--
作者：
Schickel R;Park SM;Murmann AE;Peter ME
肿瘤进展与上皮-间质转化（EMT）过程有许多共同特征。经过EMT的细胞对细胞凋亡的抵抗力增强。CD95/Fas是一种在多种组织和肿瘤细胞上表达的凋亡诱导受体。在肿瘤进展过程中，CD95经常下调，肿瘤细胞失去凋亡敏感性。miR-200 microrna抑制emt诱导的ZEB1和ZEB2转录因子。我们现在证明miR-200c使细胞对CD95介导的凋亡敏感。我们已经确定凋亡抑制剂FAP-1是miR-200c的靶标。在miR-200被抑制的细胞中，FAP-1被证明是导致cd95介导的细胞凋亡敏感性降低的原因。FAP-1作为miR-200c靶点的鉴定提供了一种分子机制，可以解释在肿瘤进展过程中miR-200表达降低的背景下观察到的CD95表达下调和细胞对CD95介导的凋亡的敏感性降低。
Tumor progression shares many characteristics with the process of epithelial-to-mesenchymal transition (EMT). Cells that have undergone an EMT are known to have an increased resistance to apoptosis. CD95/Fas is an apoptosis-inducing receptor expressed on many tissues and tumor cells. During tumor progression CD95 is frequently downregulated, and tumor cells lose apoptosis sensitivity. miR-200 microRNAs repress both the EMT-inducing ZEB1 and ZEB2 transcription factors. We now demonstrate that miR-200c sensitizes cells to apoptosis mediated by CD95. We have identified the apoptosis inhibitor FAP-1 as a target for miR-200c. FAP-1 was demonstrated to be responsible for the reduced sensitivity to CD95-mediated apoptosis in cells with inhibited miR-200. The identification of FAP-1 as a miR-200c target provides a molecular mechanism to explain both the downregulation of CD95 expression and the reduction in sensitivity of cells to CD95-mediated apoptosis that is observed in the context of reduced miR-200 expression during tumor progression.
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影响因子：
4.5
作者：
Christoffersen, Nanna Ronbjerg;Silahtaroglu, Asli;Lund, Anders H.
通讯作者：
Lund, Anders H.
影响因子：
11.2
作者：
Hurteau, Gregory J.;Carlson, J. Andrew;Brock, Graham J.
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Brock, Graham J.
影响因子：
4.8
作者：
Myc, A;Arscott, PL;Baker, JR
通讯作者：
Baker, JR
DOI：
10.1046/j.1432-1327.2000.01818.x
发表时间：
2000-12-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Nakai, Y;Irie, S;Sato, TA
通讯作者：
Sato, TA
影响因子：
4.8
作者：
Yanagisawa, J;Takahashi, M;Sato, T
通讯作者：
Sato, T