Circ-ADAM9 targeting PTEN and ATG7 promotes autophagy and apoptosis of diabetic endothelial progenitor cells by sponging mir-20a-5p

Abstract

Dysfunction of endothelial progenitor cells (EPCs) is a key factor in vascular complications of diabetes mellitus. Although the roles of microRNAs and circular RNAs in regulating cell functions have been thoroughly studied, their role in regulating autophagy and apoptosis of EPCs remains to be elucidated. This study investigated the roles of mir-20a-5p and its predicted target circ-ADAM9 in EPCs treated with high glucose (30 mM) and in a diabetic mouse hind limb ischemia model. It is found that Mir-20a-5p inhibited autophagy and apoptosis of EPCs induced by high-concentration glucose. Further, mir-20a-5p could inhibit the expression of PTEN and ATG7 in EPCs, and promote the phosphorylation of AKT and mTOR proteins under high-glucose condition. Investigation of the underlying mechanism revealed that circ-ADAM9, as a miRNA sponges of mir-20a-5p, promoted autophagy and apoptosis of EPCs induced by high-concentration glucose. Circ-ADAM9 upregulated PTEN and ATG7 in interaction with mir-20a-5p, and inhibited the phosphorylation of AKT and mTOR to aggravate autophagy and apoptosis of EPCs under high glucose. In addition, silencing of circ-ADAM9 increased microvessel formation in the hind limbs of diabetic mice. Our findings disclose a novel autophagy/apoptosis-regulatory pathway that is composed of mir-20a-5p, circ-ADAM9, PTEN, and ATG7. Circ-ADAM9 is a potential novel target for regulating the function of diabetic EPCs and angiogenesis.

Autophagy is impaired in fetal hypoplastic lungs and rescued by administration of amniotic fluid stem cell extracellular vesicles

“…We found that in hypoplastic fetal lungs at the canalicular stage, HDAC3 expression was increased compared to normal lungs and rescued to normal levels by AFSC-EV administration (Figure 3F-G). When we investigated the expression of PTEN and GATA4, which are downstream factors in the autophagy pathway and directly or indirectly regulated by the miR-17~92 cluster (34,35), we found that hypoplastic lungs had higher levels than control (Figure 3F-G). Treatment with AFSC-EVs restored PTEN expression back to control levels but had no restorative effect on GATA4 expression (Figure 3F-G).…”

RA Fibroblast-Like Synoviocytes Derived Extracellular Vesicles Promote Angiogenesis by miRNA-1972 Targeting p53/mTOR Signaling in Vascular Endotheliocyte

“…uPAR-PI3K/Akt pathway promotes tumor-like behavior of RA FLSs ( 45 ). Also, numerous studies have revealed that the activation of PI3K/Akt/mTOR pathway is involved in ECs angiogenesis ( 46 , 47 ), and p53 can suppress this pathway ( 48 ). Therefore, p53 is considered to be a key checkpoint of angiogenesis ( 49 ).…”

The Role of Epigenetic Modifications in Abdominal Aortic Aneurysm Pathogenesis

“…While their exact role in AAA formation has not been elucidated, there is evidence connecting some of these miRNAs to EC function. For example, miR-20a inhibits apoptosis of endothelial progenitor cells by targeting PTEN and ATG7 expression, while repressing endothelial migration [ 47 , 48 ]. miRNA-27a is expressed in ECs and promotes angiogenesis by negatively regulating SEMA6A, an anti-angiogenic protein [ 49 ].…”