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Published September 14, 2015 | Published + Supplemental Material
Journal Article Open

The microRNA-212/132 cluster regulates B cell development by targeting Sox4

Abstract

MicroRNAs have emerged as key regulators of B cell fate decisions and immune function. Deregulation of several microRNAs in B cells leads to the development of autoimmune disease and cancer in mice. We demonstrate that the microRNA-212/132 cluster (miR-212/132) is induced in B cells in response to B cell receptor signaling. Enforced expression of miR-132 results in a block in early B cell development at the prepro–B cell to pro–B cell transition and induces apoptosis in primary bone marrow B cells. Importantly, loss of miR-212/132 results in accelerated B cell recovery after antibody-mediated B cell depletion. We find that Sox4 is a target of miR-132 in B cells. Co-expression of SOX4 with miR-132 rescues the defect in B cell development from overexpression of miR-132 alone, thus suggesting that miR-132 may regulate B lymphopoiesis through Sox4. In addition, we show that the expression of miR-132 can inhibit cancer development in cells that are prone to B cell cancers, such as B cells expressing the c-Myc oncogene. We have thus uncovered miR-132 as a novel contributor to B cell development.

Additional Information

© 2015 Mehta et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). Submitted: 16 March 2015; Accepted: 14 August 2015. Published September 14, 2015. We thank Diana Perez at the Caltech Flow Cytometry core facility, and Igor Antoshechkin and Vijaya Kumar at the Caltech Millard and Muriel Genetics and Genomics Laboratory. We also thank Michael T. Bethune for helpful discussions throughout the preparation of this manuscript. This work was supported by funding from National Institutes of Health RO1AI079243 (D. Baltimore), National Research Service Award CA183220 (A. Mehta) and HL110691 (J.L. Zhao), the UCLA/Caltech Medical Scientist Training Program (A. Mehta and J.L. Zhao), and the Human Frontiers Science Foundation (M. Mann). The authors declare no competing financial interests.

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Published - J_Exp_Med-2015-Mehta-1679-92.pdf

Supplemental Material - JEM_20150489_sm.pdf

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August 20, 2023
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