MicroRNA let-7 regulates 3T3-L1 adipogenesis

Tingwan Sun, Mingui Fu, Angie L. Bookout, Steven A. Kliewer, David J. Mangelsdorf

Research output: Contribution to journalArticle

167 Citations (Scopus)

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 differentiationandthat itdoesso in partbytargetingHMGA2,thereby regulating the transition from clonal expansion to terminal differentiation.

Original languageEnglish (US)
Pages (from-to)925-931
Number of pages7
JournalMolecular Endocrinology
Volume23
Issue number6
DOIs
StatePublished - Jun 2009

Fingerprint

AT-Hook Motifs
3T3-L1 Cells
Adipogenesis
MicroRNAs
Adipocytes
Microarray Analysis
Growth
Transcription Factors
Messenger RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

MicroRNA let-7 regulates 3T3-L1 adipogenesis. / Sun, Tingwan; Fu, Mingui; Bookout, Angie L.; Kliewer, Steven A.; Mangelsdorf, David J.

In: Molecular Endocrinology, Vol. 23, No. 6, 06.2009, p. 925-931.

Research output: Contribution to journalArticle

Sun, Tingwan ; Fu, Mingui ; Bookout, Angie L. ; Kliewer, Steven A. ; Mangelsdorf, David J. / MicroRNA let-7 regulates 3T3-L1 adipogenesis. In: Molecular Endocrinology. 2009 ; Vol. 23, No. 6. pp. 925-931.
@article{28a76c8c1dd848b5bace71e0d275b595,
title = "MicroRNA let-7 regulates 3T3-L1 adipogenesis",
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 differentiationandthat itdoesso in partbytargetingHMGA2,thereby regulating the transition from clonal expansion to terminal differentiation.",
author = "Tingwan Sun and Mingui Fu and Bookout, {Angie L.} and Kliewer, {Steven A.} and Mangelsdorf, {David J.}",
year = "2009",
month = "6",
doi = "10.1210/me.2008-0298",
language = "English (US)",
volume = "23",
pages = "925--931",
journal = "Molecular Endocrinology",
issn = "0888-8809",
publisher = "The Endocrine Society",
number = "6",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=66449092619&partnerID=8YFLogxK

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

VL - 23

SP - 925

EP - 931

JO - Molecular Endocrinology

JF - Molecular Endocrinology

SN - 0888-8809

IS - 6

ER -