Debunking the Myth of the Endogenous Antiangiogenic Vegfaxxxb Transcripts

Debunking the Myth of the Endogenous Antiangiogenic Vegfaxxxb Transcripts

Hugues Dardente , William R English , Manoj K Valluru , Chryso Kanthou , David Simpson

Abstract

In this opinion article we critically assess evidence for the existence of a family of antiangiogenic vascular endothelial growth factor (Vegfaxxxb) transcripts, arising from the use of a phylogenetically conserved alternative distal splice site within exon 8 of the VEGFA gene. We explain that prior evidence for Vegfaxxxb transcripts in tissues rests heavily upon flawed RT-PCR methodologies, with the extensive use of 5'-tailing in primer design being the main issue. Furthermore, our analysis of large RNA-seq data sets (human and ovine) fails to identify a single Vegfaxxxb transcript. Therefore, we challenge the very existence of Vegfaxxxb transcripts, which further questions the physiological relevance of studies based on the use of 'anti-VEGFAxxxb' antibodies. Our analysis has implications for the proposed therapeutic use of isoform-specific anti-VEGFA strategies for treating cancer and retinopathies.

PubMed

Modification date : 02 August 2023 | Publication date : 20 July 2020 | Redactor : VR