MiR-92a regulates viability and angiogenesis of endothelial cells under oxidative stress

Abstract

Oxidative stress contributes to endothelial cell (EC) dysfunction, which is prevalent in ageing and atherosclerosis. MicroRNAs (miRs) are small, non-coding RNAs that post-transcriptionally regulate gene expression and play a key role in fine-tuning EC functional responses, including apoptosis and angiogenesis. MiR-92a is highly expressed in young endothelial cells in comparison with senescent endothelial cells, which exhibit increased oxidative stress and apoptosis. However, the impact of miR-92a treatment on EC viability and angiogenesis under oxidative stress is unknown. Hydrogen peroxide (H2O2) was used to induce oxidative stress in human umbilical vein endothelial cells (HUVEC). Pre-miR-92a treatment decreased H2O2–induced apoptosis of HUVEC as determined by TUNEL assay. Pre-miR-92a treatment enhanced capillary tube formation by HUVEC under oxidative stress, which was blocked by LY294002, an inhibitor of Akt phosphorylation. Interestingly, we also observed that inhibition of miR-92a by anti-miR-92a antisense can also enhance angiogenesis in HUVEC with and without oxidative stress exposure. Our results show that perturbation of miR-92a levels outside of its narrow “homeostatic” range may trigger endothelial cell angiogenesis, suggesting that the role of miR-92a in regulating angiogenesis is controversial and may vary depending on the experimental model and method of regulating miR-92a.

Function, Role, and Clinical Application of MicroRNAs in Vascular Aging

“…Wang et al reported that miR-126, the endothelial specific miRNA, enhances the proangiogenic actions of VEGF and FGF and promotes blood vessel formation by repressing the expression of Spred-1, an intracellular inhibitor of angiogenic signaling [43]. Besides, members of the miRNA-17-92 cluster also exhibit a cell-intrinsic antiangiogenic function in ECs [42, 66, 67]. For example, pre-miR-92a treatment improves HUVEC viability and preserves angiogenic capacity under oxidative stress, at least partially through the downregulation of PTEN expression [42].…”

Regulation of tumorigenesis and metastasis of hepatocellular carcinoma tumor endothelial cells by microRNA-3178 and underlying mechanism

“…Recent research has shown that the abnormal expression of miRNAs is closely related to the formation of HCC [17]. Another research reported that miRNAs regulate angiogenesis [18]. These differentially expressed miRNAs may be new antiangiogenesis targets for HCC [19].…”

Isolation of Extracellular Vesicles from Stem Cells

“…Recent evidence indicates that the transplantation of stem cells into the heart can promote cardiac repair via paracrine effects [3–7]. Stem cells can secret extracellular vesicles (EV) [8, 9], which carry noncoding RNAs, including microRNA (miRNA) and long noncoding RNA (lncRNA), which control gene expression via posttranscriptional repression [10–12] or epigenetic regulation [13]. In stem cells, noncoding RNAs have been show to play critical roles in modulating cell differentiation, proliferation, and survival [14, 15].…”