title: MicroRNA-21 regulates T-cell apoptosis by directly targeting the tumor suppressor gene Tipe2.
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.
authors.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.
authors.forename: Q
authors.initials: Q
authors.lastname: Ruan
authors.affiliation: 713 Stellar-Chance Laboratories, Department of Pathology and Laboratory of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.affiliation: 1] 713 Stellar-Chance Laboratories, Department of Pathology and Laboratory of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA [2] Shandong Eye Institute, Qingdao 266071, People's Republic of China.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.affiliation: 713 Stellar-Chance Laboratories, Department of Pathology and Laboratory of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: J
authors.initials: J
authors.lastname: Qi
authors.affiliation: 713 Stellar-Chance Laboratories, Department of Pathology and Laboratory of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: M
authors.initials: M
authors.lastname: Wei
authors.affiliation: Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
authors.forename: T
authors.initials: T
authors.lastname: Fan
authors.affiliation: 713 Stellar-Chance Laboratories, Department of Pathology and Laboratory of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: D
authors.initials: D
authors.lastname: Johnson
authors.affiliation: Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Wan
authors.affiliation: Shandong Eye Institute, Qingdao 266071, People's Republic of China.
authors.forename: W
authors.initials: W
authors.lastname: Shi
authors.affiliation: 713 Stellar-Chance Laboratories, Department of Pathology and Laboratory of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.affiliation: 713 Stellar-Chance Laboratories, Department of Pathology and Laboratory of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Y H
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014162:Transfection
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D016328:NF-kappa B; C529002:TIPE2 protein, mouse