Debunking the Myth of the Endogenous Antiangiogenic Vegfaxxxb Transcripts

Publication date: Available online 12 February 2020Source: Trends in Endocrinology & MetabolismAuthor(s): Hugues Dardente, William R. English, Manoj K. Valluru, Chryso Kanthou, David SimpsonIn 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.

Source: Trends in Endocrinology and Metabolism - February 12, 2020 Category: Endocrinology Source Type: research