Functional Deficiency of Dicer in Atherosclerosis: A Role for Hemodynamic Shear Stress Regulation of the miRNA Biogenesis Pathway
Year: 2019
Type: dissertation
Abstract: Endogenous microRNAs act as post-transcriptional gene regulators. miR-145 is significantly reduced in both human and murine atherosclerotic lesions; we have shown that re-expression of miR-145 in an atherosclerotic murine model was associated with a reduction of lesion size. Dicer is an RNase-III enzyme which cleaves pre-miRNA into mature miRNA. The regulation of Dicer and its effects on microRNAs in atherosclerosis remains undefined. Multiple atherosclerotic murine models demonstrate downregulated Dicer expression and is associated with global dysregulation of microRNAs. Investigating the mechanism behind Dicer deficiency is key to understanding atherosclerosis development. Endothelial cells (EC) from specific regions of the aorta in wild-type mice experiencing laminar or disturbed/non-laminar blood flow show differential Dicer expression. Dicer expression and function is regulated by hemodynamic shear stress in vitro. Furthermore, the presence or absence of endothelial Dicer affects expression of flow-responsive genes. We posit that Dicer deficiency can potentially prime atheroprone regions in diseased vasculature.
Source: TSpace (University of Toronto)
Author: Eileen Tran
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3156949967