MicroRNA-21 regulates T-cell apoptosis by directly targeting the tumor suppressor gene Tipe2.
MicroRNA-21 regulates T-cell apoptosis by directly targeting the tumor suppressor gene Tipe2.
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MicroRNA-21通过直接靶向肿瘤抑制基因tipe2来调节T细胞凋亡。
DOI：
10.1038/cddis.2014.47
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发表时间：
2014-02-27
影响因子：
9
通讯作者：
Chen YH
中科院分区：
文献类型：
--
作者：
Ruan Q;Wang P;Wang T;Qi J;Wei M;Wang S;Fan T;Johnson D;Wan X;Shi W;Sun H;Chen YH
MicroRNAs （MiRs）是一种短的非编码rna，可以调节基因表达。据报道，miR-21抑制活化T细胞的凋亡，但其分子机制尚不明确。肿瘤抑制因子Tipe2（或肿瘤坏死因子-α-诱导蛋白8 （TNFAIP8）样2 (TNFAIP8L2)）是新发现的TNFAIP8家族的抗炎蛋白，对维持免疫稳态至关重要。我们在这里报道，miR-21是核因子-κB的直接靶点，可以通过Tipe2编码区依赖的方式调节Tipe2的表达。在活化的T细胞和巨噬细胞中，Tipe2的表达明显下调，而miR-21的表达上调。重要的是，tipe2缺陷T细胞对凋亡的敏感性明显降低。相反，EL-4 T细胞中Tipe2的过表达增加了它们对活化诱导的凋亡的易感性。因此，Tipe2在miR-21和细胞凋亡之间提供了一个分子桥梁；miR-21至少部分通过直接靶向肿瘤抑制基因Tipe2抑制活化T细胞的凋亡。
MicroRNAs (MiRs) are short noncoding RNAs that can regulate gene expression. It has been reported that miR-21 suppresses apoptosis in activated T cells, but the molecular mechanism remains undefined. Tumor suppressor Tipe2 (or tumor necrosis factor-α-induced protein 8 (TNFAIP8)-like 2 (TNFAIP8L2)) is a newly identified anti-inflammatory protein of the TNFAIP8 family that is essential for maintaining immune homeostasis. We report here that miR-21 is a direct target of nuclear factor-κB and could regulate Tipe2 expression in a Tipe2 coding region-dependent manner. In activated T cells and macrophages, Tipe2 expression was markedly downregulated, whereas miR-21 expression was upregulated. Importantly, Tipe2-deficient T cells were significantly less sensitive to apoptosis. Conversely, overexpression of Tipe2 in EL-4 T cells increased their susceptibility to activation-induced apoptosis. Therefore, Tipe2 provides a molecular bridge between miR-21 and cell apoptosis; miR-21 suppresses apoptosis in activated T cells at least in part through directly targeting tumor suppressor gene Tipe2.
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DOI：
10.4161/cc.9.8.11202
发表时间：
2010-04-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Forman JJ;Coller HA
通讯作者：
Coller HA
影响因子：
4.8
作者：
Frankel, Lisa B.;Christoffersen, Nanna R.;Lund, Anders H.
通讯作者：
Lund, Anders H.
影响因子：
5.7
作者：
Li, Yumin;Zhu, Xuejiao;Fei, Jia
通讯作者：
Fei, Jia
影响因子：
5.3
作者：
Krichevsky AM;Gabriely G
通讯作者：
Gabriely G
影响因子：
16
作者：
Gus-Brautbar, Yael;Johnson, Derek;Zhang, Li;Sun, Honghong;Wang, Peng;Zhang, Shirley;Zhang, Lining;Chen, Youhai H.
通讯作者：
Chen, Youhai H.