Year: 2016
Type: dissertation
Abstract: Defining the roadblocks responsible for adult cardiomyocyte cell cycle arrest lies at the core of developing cardiac regenerative therapies. Inactivation of the p53/MDM2 tumor suppressor circuitry in the heart caused a significant increase in cardiomyocyte proliferation, through an upregulation of factors involved in cell cycle re-entry. These factors may be regulated by microRNAs (miRNAs), in quiescent cardiomyocytes. Therefore, we hypothesized that inactivation of p53/MDM2-regulated miRNAs could promote the expression of cell cycle activators and induce proliferation of cardiomyocytes. Comparison of miRNA expression profiles from cardiac specific p53/MDM2 double knockout (DKO) mouse hearts and wild type controls revealed 11 miRNAs that were downregulated in the "proliferative" DKO hearts and enriched for mRNA targets involved in cell cycle regulation. Knockdown of these 11 miRNAs in neonatal rat cardiomyocytes significantly increased the occurrence of cytokinesis, revealing a novel subset of p53/MDM2-regulated miRNAs responsible for maintaining cell cycle arrest in the heart.
Source: TSpace (University of Toronto)
Author: Shanna Stanley-Hasnain
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2604306183