miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130

*Department of Medicine, Biological Sciences Division, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637; and
^†College of Life Sciences, Beijing University, Beijing 10091, China

Communicated by Janet D. Rowley, University of Chicago Medical Center, Chicago, IL, January 7, 2008 (received for review October 27, 2007)

Abstract

Adipogenesis involves cell proliferation and differentiation, both of which have been shown to be regulated by micro (mi)RNA. During mouse preadipocyte 3T3L1 cell differentiation, we found that miR-17-92, a miRNA cluster that promotes cell proliferation in various cancers, was significantly up-regulated at the clonal expansion stage of adipocyte differentiation. Stable transfection of 3T3L1 cells with miR-17-92 resulted in accelerated differentiation and increased triglyceride accumulation after hormonal stimulation. By using a luciferase reporter assay, we demonstrated that miR-17-92 directly targeted the 3′ UTR region of Rb2/p130, accounting for subsequently reduced Rb2/p130 mRNA and protein quantities at the stage of clonal expansion. siRNA-mediated knock-down of Rb2/p130 at the same stage of clonal expansion recapitulated the phenotype of overexpression of miR-17-92 in the stably transfected 3T3L1 cells. These data indicate that miR-17-92 promotes adipocyte differentiation by targeting and negatively regulating Rb2/p130.

Footnotes

^‡To whom correspondence should be addressed at:
Department of Pathology and Laboratory Medicine, University of California, 1000 Veteran Avenue, Los Angeles, CA 90095.
E-mail: xinminli{at}mednet.ucla.edu
Author contributions: Q.W., Y.C.L., R.J.Q., and X.L. designed research; Q.W., Y.C.L., J.W., and Y.Q. performed research; J.K. contributed new reagents/analytic tools; X.L. analyzed data; and R.J.Q. and X.L. wrote the paper.
The authors declare no conflict of interest.