TY - JOUR
T1 - MicroRNA let-7 regulates 3T3-L1 adipogenesis
AU - Sun, Tingwan
AU - Fu, Mingui
AU - Bookout, Angie L.
AU - Kliewer, Steven A.
AU - Mangelsdorf, David J.
PY - 2009/6
Y1 - 2009/6
N2 - 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 differentiationandthat itdoesso in partbytargetingHMGA2,thereby regulating the transition from clonal expansion to terminal differentiation.
AB - 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 differentiationandthat itdoesso in partbytargetingHMGA2,thereby regulating the transition from clonal expansion to terminal differentiation.
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UR - http://www.scopus.com/inward/citedby.url?scp=66449092619&partnerID=8YFLogxK
U2 - 10.1210/me.2008-0298
DO - 10.1210/me.2008-0298
M3 - Article
C2 - 19324969
AN - SCOPUS:66449092619
SN - 0888-8809
VL - 23
SP - 925
EP - 931
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 6
ER -