MicroRNA let-7 Regulates 3T3-L1 Adipogenesis

    Authors

    T. W. Sun; M. G. Fu; A. L. Bookout; S. A. Kliewer;D. J. Mangelsdorf

    Comments

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    Abbreviated Journal Title

    Mol. Endocrinol.

    Keywords

    FACTOR HMGI-C; ADIPOCYTE DIFFERENTIATION; TRANSGENIC MICE; GENE; EXPRESSION; IDENTIFICATION; REPRESSES; PROMOTER; LIPOMAS; BINDING; Endocrinology & Metabolism

    Abstract

    Differentiation of 3T3-L1 cells into adipocytes involves a highly orchestrated series of events including clonal expansion, growth arrest, and terminal differentiation. The mechanisms coordinating these different steps are not yet fully understood. Here we investigated whether microRNAs (miRNAs) play a role in this process. Microarray analysis was performed to detect miRNA expression during 3T3-L1 preadipocyte differentiation. Several miRNAs, including let-7, were up-regulated during 3T3-L1 adipogenesis. Ectopic introduction of let-7 into 3T3-L1 cells inhibited clonal expansion as well as terminal differentiation. The mRNA encoding high-mobility group AT-hook 2 (HMGA2), a transcription factor that regulates growth and proliferation in other contexts, was inversely correlated with let-7 levels during 3T3-L1 cell adipogenesis, and let-7 markedly reduced HMGA2 concentrations. Knockdown of HMGA2 inhibited 3T3-L1 differentiation. These results suggest that let-7 plays an important role in adipocyte differentiation and that it does so in part by targeting HMGA2, thereby regulating the transition from clonal expansion to terminal differentiation. (Molecular Endocrinology 23: 925-931, 2009)

    Journal Title

    Molecular Endocrinology

    Volume

    23

    Issue/Number

    6

    Publication Date

    1-1-2009

    Document Type

    Article

    Language

    English

    First Page

    925

    Last Page

    931

    WOS Identifier

    WOS:000266403600018

    ISSN

    0888-8809

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