Regulation of vascular leak and recovery from ischemic injury by general and VE-cadherin–restricted miRNA antagonists of miR-27

Abstract

Key Points Blockmirs are designed against the miR-27 binding site in VE-cadherin and display restricted specificity. Blockmirs regulate VE-cadherin and endothelial cell junctions, inhibit edema, and promote angiogenesis associated with ischemia.

A Stromal Cell-Derived Factor 1α Analogue Improves Endothelial Cell Function in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome

“…VE-cadherin is vital for EC contacts and the prevention of vascular leak (28,29). As expected, thrombin-induced leak in HMVEC cultures was associated with a significant decline in peripheral VE-cadherin expression and increased intercellular spaces.…”

MicroRNAs and cancer: Key paradigms in molecular therapy (Review)

“…EMT transcription factors that serve as E-cadherin repressors-such as zinc finger protein (SNAI)1/SNAI2, basic helix-loop-helix proteins including E47, E2-2, Twist-related protein (TWIST)1/TWIST2, and ZEB1/ZEB2, activate cancer cells by triggering EMT (53). The miR-200 family, miR-27 and miR-205 inhibit ZEB1 and ZEB2 (54)(55)(56). In breast cancer, the expression of miR-200 is positively correlated with concentrations of E-cadherin.…”

MiRNA inhibition in tissue engineering and regenerative medicine

“…Blockmirs are ~15mer antisense oligonucleotides that are instead targeted to the mRNA and function to target and block miRNA binding sites (Figure 1G) [25]. These molecules bind to untranslated regions of mRNA where miRNA bind, thus blocking miRNA-induced mRNA degradation while retaining the ability of the mRNA to be translated into protein [26].…”

“…Blockmirs are ~15mer antisense oligonucleotides that are instead targeted to the mRNA and function to target and block miRNA binding sites (Figure 1G) [25]. These molecules bind to untranslated regions of mRNA where miRNA bind, thus blocking miRNA-induced mRNA degradation while retaining the ability of the mRNA to be translated into protein [26]. In a recent application of a blockmir designed against the miR-27 binding site on VE-cadherin mRNA, the authors achieved selective up-regulation of VE-cadherin but not two other verified miR-27 targets, PPARγ and SEMA6A.…”