| Autor: |
Gurtan AM; David H. Koch Institute for Integrative Cancer Research, Cambridge, Massachusetts 02139, USA., Ravi A, Rahl PB, Bosson AD, JnBaptiste CK, Bhutkar A, Whittaker CA, Young RA, Sharp PA |
| Jazyk: |
angličtina |
| Zdroj: |
Genes & development [Genes Dev] 2013 Apr 15; Vol. 27 (8), pp. 941-54. |
| DOI: |
10.1101/gad.215376.113 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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