MicroRNA let-7i induced autophagy to protect T cell from apoptosis by targeting IGF1R
MicroRNA let-7i induced autophagy to protect T cell from apoptosis by targeting IGF1R
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MicroRNA let-7i 通过靶向 IGF1R 诱导自噬，保护 T 细胞免于凋亡
DOI：
10.1016/j.bbrc.2014.10.002
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发表时间：
2014-10-31
影响因子：
3.1
通讯作者：
Lin, Yanliang
中科院分区：
文献类型：
--
作者：
Hou, Chunfeng;Zhu, Mengzhu;Lin, Yanliang
MicroRNA let-7i在强直性脊柱炎（AS）患者的T细胞中上调。在这项研究中，我们研究了let-7i在T细胞存活中的作用。我们的研究结果表明，下调胰岛素样生长因子-1受体（IGF 1 R）的T细胞与AS患者。荧光素酶报告基因分析表明IGF 1 R是let-7i的直接靶点。let-7i在Jurkat细胞中的过表达显著抑制IGF 1 R的表达，这模拟了IGF 1 R siRNA的作用。IGF 1 R抑制导致mTOR和Akt磷酸化急剧下降，Bcl-2下调，Bax上调以及caspase 3和PARP的切割。同时，IGF 1 R抑制诱导自噬。let-7i过表达诱导的自噬有助于保护细胞免于凋亡。我们的数据表明let-7i可能通过靶向IGF 1 R来控制AS中T细胞的命运。(C)2014 Elsevier Inc. All rights reserved.
MicroRNA let-7i is up-regulated in T cells from patients with Ankylosing Spondylitis (AS). In this study, we investigated the role of let-7i in T cells survival. Our results demonstrated down-regulation of insulin-like growth factor-1 receptor (IGF1R) in T cells from patients with AS. Luciferase reporter assay suggested IGF1R as direct target of let-7i. Overexpression of let-7i in Jurkat cells significantly suppressed IGF1R expression, which mimicked the action of IGF1R siRNA. IGF1R inhibition led to a strinking decrease in phosphorylation of mTOR and Akt, down-regulation of Bcl-2, up-regulation of Bax and cleavage of caspase 3 and PARP. Meanwhile, IGF1R inhibition induced autophagy. Autophagy induced by let-7i overexpression contributed to protect cells from apoptosis. Our data indicated that let-7i might control T cells fates in AS by targeting IGF1R. (C) 2014 Elsevier Inc. All rights reserved.