Long non‑coding RNA GAS5 regulates myocardial ischemia‑reperfusion injury through the PI3K/AKT apoptosis pathway by sponging miR‑532‑5p

Abstract

Long non-coding RNAs (lncRNAs) have been revealed to have a marked effect in cardiovascular diseases, including during cardiac development, cardiac hypertrophy, myocardial fibrosis and myocardial ischemic injury. The mechanism of myocardial ischemia-reperfusion injury (MIRI) is very complicated. Although studies have confirmed that lncRNAs are involved, the specific mechanism remains largely unknown. The lncRNA growth arrest specific 5 (GAS5) is known as a regulator of a number of diseases, including certain cancer types. The present study aimed to investigate the function of lncRNA GAS5 in MIRI. The present study reported that the expression of lncRNA GAS5 in H9c2 cells treated with anoxia and reoxygenation was significantly upregulated compared with the control group (P<0.05). Similarly, the expression of lncRNA GAS5 in myocardial tissue obtained from rats treated with MIRI was significantly upregulated compared with the untreated controls (P<0.05). Silencing of lncRNA GAS5 was able to attenuate myocardial damage, as cell viability increased and the apoptosis rate decreased. classical apoptotic proteins involved in MIRI, including B-cell lymphoma 2, Bcl-2-associated X protein and cleaved caspase-3, also exhibited the same trend. At the same time, when lncRNA GAS5 was silenced, microRNA (miR)-532-5p, which was originally expressed at the stage of injury, was upregulated. The luciferase reporter assay results indicated that the lncRNA GAS5 functioned as a molecular sponge of miR-532-5p. The gain-and loss-of-function analysis of miR-532-5p indicated that it was involved in the regulation of MIRI; the trend of results following its overexpression was also consistent with the trend observed following the silencing of lncRNA GAS5. Notably, the protective effect of lncRNA GAS5 silencing on cells was attenuated by miR-532-5p inhibition. Phosphatase and tensin homolog was revealed to be a key target gene for the function of lncRNA GAS5, and its regulation was achieved via binding to miR-532-5p. In other words, silencing lncRNA GAS5 ultimately promoted the activation of the phosphoinositide-3-kinase (PI3K)/protein kinase B pathway (AKT) to reduce myocardial damage. Therefore, lncRNA GAS5 was able to regulate MIRI through the PI3K/AKT apoptosis pathway by sponging miR-532-5p.

LncRNA TUG1 competitively binds to miR‐340 to accelerate myocardial ischemia‐reperfusion injury

“…4 Moreover, the dysregulation of the lncRNAs expression and its downstream effects on expression of miRNAs has also been highlighted as a possible modulating commodity in the occurrence of MIRI. 23,24 The current study introduced the effects of lncRNA TUG1 on MIRI in vitro and in vivo, emphasizing the mechanisms of TUG1 associated with the miR-340/HDAC4/β-catenin/GLUT1 axis ( Figure 6). Additionally, previous studies have proven that lncRNA TUG1 expresses at a high level in MIRI and its overexpression functions as a promoter of cardiomyocyte apoptosis and autophagy as well as myocardial infraction.…”

Study on Targeting Relationship Between miR-320b and FGD5-AS1 and Its Effect on Biological Function of Osteosarcoma Cells

“…Increasing evidence has demonstrated that lncRNAs, highly expressed in the cytoplasm, can act as molecular sponges, competitively bind or adsorb with other regulatory proteins and miRNAs, thus participating in the biological processes of tumors. 29 , 30 In this study, we predicted the lncRNA-miRNA binding sites through three biological target prediction sites: starBase, lncRNASNP2, and Diana. A total of 4 shared miRNAs were screened out, of which miR-320b belonged to the miR-320 family, which showed a correlation with osteosarcoma in previous reports.…”

GAS5‑mediated regulation of cell signaling (Review)

“…Inhibiting the expression of GAS5 activates the PI3K/AKT signaling pathway and increases the expression of its downstream proteins matrix metallopeptidase 9 and tumor protein p53 in human trophoblast cell lines HTR-8/SVneo and JEG-3 ( 75 ). GAS5 competitively binds to miR-532-5p such that silencing GAS5 expression upregulates the expression of miR-532-5p to activate the PI3K/AKT signaling pathway in myocardial ischemia reperfusion injury ( 76 ). This indicates that GAS5 regulates the PI3K/AKT signaling pathway by binding with miR-532-5p ( 76 ).…”

“…GAS5 competitively binds to miR-532-5p such that silencing GAS5 expression upregulates the expression of miR-532-5p to activate the PI3K/AKT signaling pathway in myocardial ischemia reperfusion injury ( 76 ). This indicates that GAS5 regulates the PI3K/AKT signaling pathway by binding with miR-532-5p ( 76 ). Furthermore, in ischaemic brain injury, GAS5 enhances the expression level of PTEN by regulating the expression of miR-21, thereby inhibiting the PI3K/AKT signaling pathway ( 77 ).…”