Journal
CELL CYCLE
Volume 12, Issue 22, Pages 3537-3546Publisher
LANDES BIOSCIENCE
DOI: 10.4161/cc.26592
Keywords
microRNA; senescence; BMI1; miR-141; polycomb group proteins; aging
Categories
Funding
- National Cancer Institute, NIH [RO1 CA094150]
- Office of the Provost
- Office of the Vice President for Research, George Washington University
Ask authors/readers for more resources
Polycomb group protein BMIl is an important regulator of senescence, aging, and cancer. On one hand, it is overexpressed in cancer cells and is required for self-renewal of stem cells. On the other hand, it is downregulated during senescence and aging. MicroRNAs have emerged as major regulators of almost every gene associated with cancer, aging, and related pathologies. At present, very little is known about the miRNAs that regulate the expression of BMIl. Here, we report that miR-141 posttranscriptionally downregulates BMI1 expression in human diploid fibroblasts (HDFs) via a miR141 targeting sequence in the 3' untranslated region of BMIl mRNA. We also show that overexpression of miR-141 induces premature senescence in HDFs via targeting of BMII in normal but not in exogenous BM11-overexpressing HDFs. Induction of premature senescence in HDFs was accompanied by upregulation of p16INK4a, an important downstream target of BMI1 and a major regulator of senescence. Our results suggest that miR-141-based therapies could be developed to treat pathologies where BMIl is deregulated.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available