title: 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.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125 David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: Arnav
authors.initials: A
authors.lastname: Mehta
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Mati
authors.initials: M
authors.lastname: Mann
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125 David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: Jimmy L
authors.initials: JL
authors.lastname: Zhao
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Georgi K
authors.initials: GK
authors.lastname: Marinov
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Devdoot
authors.initials: D
authors.lastname: Majumdar
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Garcia-Flores
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Xiaomi
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, Gottingen 37077, Germany.
authors.forename: Erdem
authors.initials: E
authors.lastname: Erikci
authors.affiliation: Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, Gottingen 37077, Germany.
authors.forename: Kamal
authors.initials: K
authors.lastname: Chowdhury
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125 baltimo@caltech.edu.
authors.forename: David
authors.initials: D
authors.lastname: Baltimore
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001402:B-Lymphocytes / Q000473:pathology / Q000502:physiology*; D002470:Cell Survival; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D015448:Leukemia, B-Cell / Q000235:genetics; D007942:Leukemia, Experimental / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D055751:SOXC Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C546976:MIRN132 microRNA, mouse; C554518:MIRN212 microRNA, mouse; D035683:MicroRNAs; D055751:SOXC Transcription Factors; C489990:Sox4 protein, mouse