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Genes Dev. 2013 Apr 15;27(8):941-54. doi: 10.1101/gad.215376.113.

Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts.

Author information

1
David H. Koch Institute for Integrative Cancer Research, Cambridge, Massachusetts 02139, USA.

Abstract

MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to derepression of let-7 targets at levels that exceed 10-fold to 100-fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 (E3.5) and the induction of let-7 upon differentiation at E10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor-suppressive function.

PMID:
23630078
PMCID:
PMC3650230
DOI:
10.1101/gad.215376.113
[Indexed for MEDLINE]
Free PMC Article

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