title: Regulation of T lymphocyte activation by microRNA-21.
abstract: MicroRNAs are small noncoding RNAs that act as posttranscriptional regulators of gene expression. To identify microRNAs involved in T cell activation, we performed a microRNA array profiling with Jurkat cells. We found that microRNA-21 (miR-21), which is upregulated in many tumors by targeting a series of tumor suppressor genes to promote tumor growth, was significantly increased in activated Jurkat cells and primary CD4(+) T lymphocytes compared with that in quiescent counterparts. By using a signaling network building tool, miR-21 was predicted regulates ERK and JNK signaling in activated Jurkat cells. Indeed, miR-21 promotes ERK and JNK signaling in activated T cells. Sprouty1, a direct target of miR-21 that has been shown an inhibitor of ERK and JNK, was also inhibited by forced miR-21 expression in activated T cells. Reciprocally, miR-21 levels were induced by MEK or JNK signaling response to T cell receptor (TCR) engagement. Furthermore, transfection with miR-21 mimic promotes activator protein 1 (AP-1) activity and interleukin-2 (IL-2) expression. These results provide a missing function of miR-21 in TCR-mediated signaling transduction in T lymphocytes, suggesting that miR-21 may augment T cell immune response by a positive feedback mechanism.
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, PR China.
authors.forename: Liangqiang
authors.initials: L
authors.lastname: He
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, PR China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, PR China.
authors.forename: Yongzhe
authors.initials: Y
authors.lastname: Ren
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, PR China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, PR China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, PR China. Electronic address: chengwe@outlook.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, PR China; Changzhou High-Tech Research Institute of Nanjing University, Changzhou City, PR China; Jiangsu TargetPharma Laboratories Inc., Changzhou City, PR China. Electronic address: zchua@nju.edu.cn.
authors.forename: Zi-Chun
authors.initials: ZC
authors.lastname: Hua
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism*; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D007376:Interleukin-2; C524940:MIRN21 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; C486055:SPRY1 protein, human; D018808:Transcription Factor AP-1; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases
keywords: ERK; Interleukin-2; JNK; MicroRNA; T cell activation