MicroRNA-21 regulates T-cell apoptosis by directly targeting the tumor suppressor gene Tipe2 |
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Authors: | Q Ruan P Wang T Wang J Qi M Wei S Wang T Fan D Johnson X Wan W Shi H Sun Y H Chen |
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Affiliation: | 1.Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People''s Republic of China;2.713 Stellar-Chance Laboratories, Department of Pathology and Laboratory of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA;3.Shandong Eye Institute, Qingdao 266071, People''s Republic of China |
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Abstract: | 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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Keywords: | MiR-21, TNFAIP8, Tipe2, apoptosis, NF-κ B |
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