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Papers In Press, published online ahead of print October 25, 2004
J. Biol. Chem, 10.1074/jbc.C400438200
Submitted on September 16, 2004
Revised on October 25, 2004
Accepted on October 25, 2004

MicroRNA-143 regulates adipocyte differentiation

Christine Esau, Xiaolin Kang, Eigen Peralta, Elaine Hanson, Eric G Marcusson, Lingamanaidu V Ravichandran, Yingqing Sun, Seongjoon Koo, Ranjan J Perera, Ravi Jain, Nicholas M Dean, Susan M Freier, C. Frank Bennett, Bridget Lollo, and Richard Griffey

Isis Pharmaceuticals, Carlsbad, CA 92008

Corresponding Author: cesau{at}isisph.com

microRNAs (miRNAs) are endogenously expressed 20-22 nucleotide RNAs thought to repress protein translation through binding to a target mRNA. Only a few of the more than 250 predicted human miRNAs have been assigned any biological function. In an effort to uncover miRNAs important during adipocyte differentiation, antisense oligonucleotides (ASOs) targeting 86 human miRNAs were transfected into cultured human pre-adipocytes and their ability to modulate adipocyte differentiation was evaluated. Expression of 254 miRNAs in differentiating adipocytes was also examined on a miRNA microarray. Here we report that the combination of expression data and functional assay results identified a role for miR-143 in adipocyte differentiation. miR-143 levels increased in differentiating adipocytes, and inhibition of miR-143 effectively inhibited adipocyte differentiation. In addition, protein levels of the proposed miR-143 target ERK5 were higher in ASO-treated adipocytes. These results demonstrate that miR-143 is involved in adipocyte differentiation, and may act through target gene ERK5.


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