PRC, INRA, CNRS, IFCE, Université de Tours, 37380 Nouzilly, France.
Department of Oncology and Metabolism, Tumour Microcirculation Group, University of Sheffield, School of Medicine, Beech Hill Road, Sheffield, S10 2RX, UK.
Trends Endocrinol Metab. 2020 Jun;31(6):398-409. doi: 10.1016/j.tem.2020.01.014. Epub 2020 Feb 12.
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.
在这篇观点文章中，我们批判性地评估了血管内皮生长因子 (Vegfaxxxb) 转录物家族存在的证据，这些转录物是由 VEGFA 基因第 8 外显子中使用进化上保守的替代远端剪接位点产生的。我们解释说，组织中 Vegfaxxxb 转录物的先前证据主要依赖于有缺陷的 RT-PCR 方法，其中引物设计中广泛使用 5'-加尾是主要问题。此外，我们对大型 RNA-seq 数据集（人类和绵羊）的分析未能确定单个 Vegfaxxxb 转录物。因此，我们质疑 Vegfaxxxb 转录物的存在，这进一步质疑了基于使用“抗-VEGFAxxxb”抗体的研究的生理相关性。我们的分析对拟议的使用同种型特异性抗 VEGFA 策略治疗癌症和视网膜病变的治疗应用具有影响。
