LncRNA FGD5-AS1 acts as a competing endogenous RNA for miRNA-223 to lessen oxygen-glucose deprivation and simulated reperfusion (OGD/R)-induced neurons injury

Abstract

The purpose of this study was to evaluate whether FGD5-AS1 participates in oxygen-glucose deprivation and simulated reperfusion (OGD/R)-induced neurons injury and the detailed mechanism. An OGD/R model was established using the primary cortical neuron isolated from the brains of Sprague-Dawley rats. qRT-PCR and western blot were performed to detect the RNA and protein expression levels, respectively. Cell counting kit 8 (CCK8) and flow cytometry assays were used to evaluate the proliferation and apoptosis of neurons. The luciferase reporter assay was used to verify the interaction between lncRNA FGD5-AS1 and miRNA-223. We found that the expression of FGD5-AS1 is decreased in neurons suffering from OGD/R. Up-regulation of FGD5-AS1 could recover proliferation and inhibit apoptosis of OGD/R-injured neurons. In addition, the interaction between FGD5-AS1 and miRNA-223 were verified. The expression of miRNA-223 was negatively correlated with the level of FGD5-AS1. In turn, the expression of insulin-like growth factor-1 receptor (IGFIR, a target gene of miR-223) was positively associated with the level of FGD5-AS1. Simultaneously down-regulating miR-223 and over-expressing FGD5-AS1 as well as IGF1R exhibited an additional effect of extenuating OGD/R damage i.e. increasing neuron proliferation and reducing neuron apoptosis. In conclusion, our findings indicated that FGD5-AS1 may protect the neuron against OGD/R injury via acting as a ceRNA for miR-223 to mediate IGF1R expression, which contributes to a deeper understanding of ischemic stroke and provide a promising therapeutic target for this disease.

LncRNA FGD5‐AS1 enhances the proliferation and stemness of hepatocellular carcinoma cells through targeting miR‐223 and regulating the expression of ECT2 and FAT1

“…As FGD5‐AS1 has been reported to target miR‐223 in neurons, 18 we analyzed whether FGD5‐AS1 targeted miR‐223 in HCC cells. The binding site for miR‐223 in FGD5‐AS1 was shown in Figure 4a.…”

“…Growing evidences have shown vital roles of the lncRNA‐miRNA‐mRNA competing endogenous RNA (ceRNA) interaction network in human carcinomas 17 . The observations that FGD5‐AS1 directly targets microRNA‐223 (miR‐223) in neurons 18 and miR‐223 is a key regulator in HCC 19 imply that FGD5‐AS1 might regulate HCC progression via targeting miR‐223. Epithelial cell transforming sequence 2 (ECT2) and FAT atypical cadherin 1 (FAT1) are identified as novel targets of miR‐223 recently 20,21 .…”

Long Non-Coding RNA-Mediated Competing Endogenous RNA Networks in Ischemic Stroke: Molecular Mechanisms, Therapeutic Implications, and Challenges

“…Jing et al also found that overexpression of LncRNA mu-1-opioid peptide receptor (Oprm1) results in the alleviation of apoptosis from cerebral I/R injury through the Oprm1/miR-155/GATA binding protein 3 (GATA3) axis ( Jing et al, 2019 ). Furthermore, the LncRNA AK038897/miR-26a-5p/death-associated protein kinase 1 (DAPK1), FGD5 antisense RNA 1 (FGD5-AS1)/miRNA-223/insulin-like growth factor (IGF)-1 receptor (IGF1R), tumor-associated LncRNA expressed on chromosome 2 (TALNEC2)/miR-650/apoptotic peptidase activating factor 1 (APAF1), FOXD3-AS1/miR-765/BCL2L13, and RNA imprinted and accumulated in nucleus (Rian)/miR-144-3p/GATA3 axes have been found to attenuate apoptosis after cerebral I/R injury ( Zhang XQ. et al, 2019 ; Wei et al, 2019 ; Lu et al, 2020 ; Yao et al, 2020 ; Chen M. et al, 2021 ; Cao et al, 2021 ).…”

Diagnostic significance of serum FGD5-AS1 and its predictive value for the development of cardiovascular diseases in patients with type 2 diabetes

“…FGD5-AS1 has been discovered to attenuate hypoxia-induced oxidative stress and apoptosis in human cardiomyocytes [ 29 ]. FGD5-AS1 has also exhibited an effect of extenuating oxygen–glucose deprivation and simulated reperfusion damage by increasing neuron proliferation but reducing neuron apoptosis [ 30 ]. In this study, FGD5-AS1 displayed an effect on the proliferation and apoptosis of human primary ventricular cardiomyocytes (AC16) and aortic vascular smooth muscle cells (HA-VSMC).…”