1. MiR-210 Is Induced by Oct-2, Regulates B Cells, and Inhibits Autoantibody Production.
- Author
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Yingting Mok, Schwierzeck, Vera, Thomas, David C., Vigorito, Elena, Rayner, Tim F., Jarvis, Lorna B., Prosser, Haydn M., Bradley, Allan, Withers, David R., Mårtensson, Inga-Lill, Corcoran, Lynn M., Blenkiron, Cherie, Miska, Eric A., Lyons, Paul A., and Smith, Kenneth G. C.
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MICRORNA , *B cells , *AUTOANTIBODIES , *TRANSCRIPTION factors , *GENETIC overexpression , *CELL proliferation , *CELL cycle - Abstract
MicroRNAs (MiRs) are small, noncoding RNAs that regulate gene expression posttranscriptionally. In this study, we show that MiR-210 is induced by Oct-2, a key transcriptional mediator of B cell activation. Germline deletion of MiR-210 results in the development of autoantibodies from 5 mo of age. Overexpression of MiR-210 in vivo resulted in cell autonomous expansion of the B1 lineage and impaired fitness of B2 cells. Mice overexpressing MiR-210 exhibited impaired class-switched Ab responses, a finding confirmed in wild-type B cells transfected with a MiR-210 mimic. In vitro studies demonstrated defects in cellular proliferation and cell cycle entry, which were consistent with the transcriptomic analysis demonstrating downregulation of genes involved in cellular proliferation and B cell activation. These findings indicate that Oct-2 induction of MiR-210 provides a novel inhibitory mechanism for the control of B cells and autoantibody production. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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