Identification of Care-binding Micrornas Targeting Vegfa and the Role of Hnrnp L in Modulation of Their Activities
Year: 2011
Type: article
Abstract: FAEGHEH JAFARIFAR Expression of vascular endothelial growth factor A (VEGFA) by tumor-associated macrophages (TAMs) is critical for tumor progression and metastasis.Hypoxic microenvironment of solid tumors induces VEGFA expression in TAMs by increased transcription and mRNA stabilization.VEGFA mRNA stabilization mediated by RNA binding proteins (RBPs) such as heterogeneous nuclear ribonucleoprotein L (hnRNP L) plays a major role in VEGFA regulation.hnRNP L binds to a specific CA-rich element (CARE) in the VEGFA 3'-untranslated region (3'-UTR).Our laboratory has identified an RNA conformational switch in human VEGFA 3'-UTR that integrates signals from interferon gamma (IFN-γ) and hypoxia to regulate VEGFA expression in human macrophage-like monocytic cells.The RNA conformational change in adjoining elements GAIT (IFN-γ-activated inhibitor of translation) and CARE is dictated by mutually exclusive, stimulus-dependent binding of proteins.These proteins include the heterotetrameric IFN γ-activated inhibitor of translation complex (GAIT) and hnRNP L.This dissertation is focused on the interplay between microRNAs (miRNAs) and RBP that regulates the expression of one of the most important angiogenic factors VEGFA.We identified a new mechanism of stress-dependent VEGFA regulation that involves
Author: Faegheh Jafarifar
Institution: Case Western Reserve University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2277269916