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Journal Article

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

MPS-Authors
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Erikci,  E.
Facility of Microarray Analyses, MPI for biophysical chemistry, Max Planck Society;

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Chowdhury,  K.
Facility of Microarray Analyses, MPI for biophysical chemistry, Max Planck Society;

Fulltext (public)

2234930.pdf
(Publisher version), 3MB

Supplementary Material (public)

2234930_Suppl.pdf
(Supplementary material), 427KB

Citation

Mehta, A., Mann, M., Zhao, J. L., Marinov, G. K., Majumdar, D., Garcia-Flores, Y., et al. (2015). The microRNA-212/132 cluster regulates B cell development by targeting Sox4. Journal of Experimental Medicine, 212(10), 1679-1692. doi:10.1084/jem.20150489.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0029-24CE-2
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.