Year: 2013
Type: preprint
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.
Source: Genes & Development
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
Awards: Regulation of mRNA Processing, G2360436881, G2478825566, Stress and Proliferation States Impact MicroRNA-Mediated Regulation in Cancer, Medical Scientist Training Program, Characterization of Pathways Controlling Cancer at the Level of Gene Regulation, G4774430914, G5040728435, G5059120797, Transcriptional Regulatory Networks in Living Cells, G7720012928, G9000060701, G9000076494, G9000281291, Cancer Center Support (Core) Grant, G941982536, G984565768
OpenAlex ID: W7074131417