A microRNA network regulates proliferative timing and extracellular matrix synthesis during cellular quiescence in fibroblasts

Genome Biology

Hilary A Coller¹  Eric S Silberman¹  Mina Kojima¹  Joshua J Forman¹  Talia R Chapman¹  Johanna MS Lemons¹  Elizabeth L Johnson¹  Aster Legesse-Miller¹  Matthew Y Remillard¹  Eric J Suh¹ 

[1] Princeton University, Department of Molecular Biology, 14 Washington Rd, Princeton, NJ 08544 USA

关键词: miR-29;    Microarray;    Fibroblast;    Extracellular matrix;    Proliferation;    Cell cycle;    Quiescence;    MicroRNA;   

Others  :  866942
DOI  :  10.1186/gb-2012-13-12-r121

 received in 2012-07-09, accepted in 2012-12-22,  发布年份 2012

【 摘 要 】

Background

Although quiescence (reversible cell cycle arrest) is a key part in the life history and fate of many mammalian cell types, the mechanisms of gene regulation in quiescent cells are poorly understood. We sought to clarify the role of microRNAs as regulators of the cellular functions of quiescent human fibroblasts.

Results

Using microarrays, we discovered that the expression of the majority of profiled microRNAs differed between proliferating and quiescent fibroblasts. Fibroblasts induced into quiescence by contact inhibition or serum starvation had similar microRNA profiles, indicating common changes induced by distinct quiescence signals. By analyzing the gene expression patterns of microRNA target genes with quiescence, we discovered a strong regulatory function for miR-29, which is downregulated with quiescence. Using microarrays and immunoblotting, we confirmed that miR-29 targets genes encoding collagen and other extracellular matrix proteins and that those target genes are induced in quiescence. In addition, overexpression of miR-29 resulted in more rapid cell cycle re-entry from quiescence. We also found that let-7 and miR-125 were upregulated in quiescent cells. Overexpression of either one alone resulted in slower cell cycle re-entry from quiescence, while the combination of both together slowed cell cycle re-entry even further.

Conclusions

microRNAs regulate key aspects of fibroblast quiescence including the proliferative state of the cells as well as their gene expression profiles, in particular, the induction of extracellular matrix proteins in quiescent fibroblasts.

【 授权许可】

   
2012 Suh et al.; licensee BioMed Central Ltd.

【 图 表 】

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