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LINC00607 facilitates endothelial VEGF-A receptor FLT1 splicing - PubMed

3 hours ago
  • #FLT1 splicing
  • #preeclampsia
  • #LINC00607
  • LINC00607 is a long non-coding RNA that regulates alternative splicing of the VEGF receptor FLT1 in endothelial cells, influencing angiogenesis.
  • Knockout of LINC00607 increases production of soluble FLT1 (sFLT1), a decoy receptor that inhibits VEGF signaling and impairs angiogenesis, which can be reversed with sFLT1-neutralizing antibodies.
  • LINC00607 interacts with U2 snRNA and depends on the chromatin remodeler BRG1 to prevent exon 15 inclusion in FLT1, thus reducing sFLT1 formation.
  • A splice-blocking morpholino targeting the FLT1 intron14/exon15 junction reduces sFLT1 production and enhances VEGF-A-mediated sprouting by interacting with LINC00607 and U2 snRNA.
  • LINC00607 expression is downregulated in preeclampsia and inversely correlates with sFLT1 levels in vascular diseases, suggesting a role in the pathophysiology of conditions like preeclampsia.