Long Noncoding RNA SCIRT Promotes HUVEC Angiogenesis via Stabilizing VEGFA mRNA Induced by Hypoxia

Abstract

Ischemia-reperfusion injury (IRI) is closely associated the abnormal expression of long noncoding RNAs (lncRNAs), especially for their regulatory roles in IRI-related angiogenesis. This study applied a hypoxia-reoxygenation (HR) cell model to simulate the IRI condition, as well as RNA sequencing and RNA pull-down experiments to reveal roles of the lncRNA and Stem Cell Inhibitory RNA Transcript (SCIRT), in endothelial angiogenesis. We found that SCIRT was increased under the HR condition and exhibited a high expression correlation with angiogenesis marker VEGFA. RNA-seq data analysis further revealed that VEGFA-related angiogenesis was regulated by SCIRT in HUVECs. Gain and loss of function experiments proved that SCIRT posttranscriptionally regulated VEGFA via affecting its mRNA stability. Furthermore, HuR (ELAVL1), an RNA binding protein (RBP), was identified as a SCIRT-binding partner, which bound and stabilized VEGFA. Moreover, SCIRT promoted HuR expression posttranslationally by inhibiting its ubiquitination under the HR condition. These findings reveal that lncRNA SCIRT can mediate endothelial angiogenesis by stabilizing the VEGFA mRNA via modulating RBP HuR stability under the HR condition.

Single-cell insights: pioneering an integrated atlas of chromatin accessibility and transcriptomic landscapes in diabetic cardiomyopathy

“…Previous research has suggested their relevance to heart diseases [26]. For example, VEGF-A is key in triggering cardiac angiogenic responses after acute myocardial infarction via regulating its interactors or downstream factors [27,28]. The results indicated that both endothelial cell-0 and endothelial cell-1 exhibited interactions with myocardial cells and fibroblasts involving receptors such as PDGFB_LRP1, PROS1_AXL, PDGFB_PDGFRA, PDGFB_PDGFRB, and PDGFB_ PDGFR (Fig.…”

Cancer Metabolism and Ischemia-Reperfusion Injury: Two Sides of the Same Coin

“…For example, in the kidney, VEGF is predominantly expressed in tubular epithelial cells, and VEGFR are mostly seen in cells of the preglomerular, glomerular and peritubular areas of the kidney. [ 67 ] Additionally, because it simultaneously increases microvascular permeability and contributes to endothelial cell migration, it has the potential to reduce IRI [ 68 ].…”

Vitexin Regulates Angiogenesis and Osteogenesis in Ovariectomy-Induced Osteoporosis of Rats via the VDR/PI3K/AKT/eNOS Signaling Pathway

“…6 Hypoxia is a common pathological process of bone diseases, and osteoporosis results in local hypoxia in bone, affecting bone reconstruction, bone repair, and blood circulation. Hypoxia exposure attenuated the protein expression of CD31, 7 VEGFA, 8 and eNOS 9 in endothelial cells, which inhibits the proliferation, migration ability, and tube formation of endothelial cells. Therefore, up-regulating the expression of eNOS may be a key link in promoting angiogenesis.…”