Abstract
Ischemic stroke (IS) is a common cerebrovascular disease characterized by insufficient blood blow to the brain and the second leading cause of death as well as disability worldwide. Recent literatures have indicated that abnormal expression of miR-339 is closely related to IS. In this study, we attempted to assess the biological function of miR-339 and its underlying mechanism in IS. By accessing the GEO repository, the expression of miR-339, FGF9, and CACNG2 in middle cerebral artery occlusion (MCAO) and non-MCAO was evaluated. PC12 cells after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment were prepared to mimic in vitro the IS model. The levels of miR-339, FGF9, CACNG2, and MAPK-related markers were quantitatively measured by qRT-PCR and Western blot. CCK-8 and flow cytometry analyses were performed to examine cell viability and apoptosis, respectively. IS-related potential pathways were identified using KEGG enrichment analysis and GO annotations. Bioinformatics analysis and dual-luciferase reporter assay were used to predict and verify the possible target of miR-339. Our results showed that miR-339 expression was significantly increased in MCAO and OGD/R-treated PC12 cells. Overexpression of miR-339 inhibited cell viability of PC12 cells subjected to OGD/R treatment. FGF9 and CACMG2 are direct targets of miR-339 and can reverse the aggressive effect of miR-339 on the proliferation and apoptosis of OGD/R-treated PC12 cells. Moreover, miR-339 mediated the activation of the MAPK pathway, which was inhibited by the FGF9/CACNG2 axis in PC12 cells treated by OGD/R stimulation. In summary, these findings suggested that miR-339 might act as a disruptive molecule to accelerate the IS progression via targeting the FGF9/CACNG2 axis and mediating the MAPK pathway.
Highlights
Ischemic stroke (IS) is a common neurological disease with high recurrence or disability rate [1, 2]
To inquire the biological function of miR-339 in IS, we firstly analyzed the expression of miR-339 in middle cerebral artery occlusion (MCAO) and normal tissues based on the Gene Expression Omnibus (GEO) datasets. miR-339 was expressed at a higher level in MCAO samples compared with the control (Figure 1A, P < 0.05)
Results indicated that the oxygen-glucose deprivation/reoxygenation (OGD/R) treatment significantly attenuated the proliferation of PC12 cells; up-regulation of miR-339 further induced a decrease in the proliferation of PC12 cells after OGD/R stimulation compared with miR339 mimic NC group, whereas down-regulation of miR-339 remarkably elevated the proliferative ability of PC12 cells (Figure 1C, P < 0.01)
Summary
Ischemic stroke (IS) is a common neurological disease with high recurrence or disability rate [1, 2]. Increasing statistical evidence has demonstrated that IS accounts for 80% of all strokes and seriously damages human health and life [4]. The most efficacious treatment of IS is thrombolysis with reperfusion at the appropriate time [5]. This treatment tends to induce cerebral ischemia reperfusion injury through enforcing inflammation and glutamate excitotoxicity [6, 7]. It is of great significance to decipher potential therapeutic targets and effective treatment options for IS
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
