MicroRNA-21 regulates T-cell apoptosis by directly targeting the tumor suppressor gene Tipe2.

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

Cell death & disease 2014 Feb 27

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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.

Citation

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. MicroRNA-21 regulates T-cell apoptosis by directly targeting the tumor suppressor gene Tipe2. Cell death & disease. 2014 Feb 27;5:e1095