LncRNA FOXD3-AS1 knockdown protects against cerebral ischemia/reperfusion injury via miR-765/BCL2L13 axis - 18/11/20
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Graphical abstract |
The up-regulated FOXD3-AS1 sponged miR-765 to elevate the expression of BCL2L13, resulting in cell apoptosis through increasing the expression of BAX, c-PARP and c-caspase-3 and decreasing the expression of Bcl-2 after cerebral ischemia, leading to ischemia brain injury. Whereas, FOXD3-AS1 inhibition or miR-765 overexpression could alleviate cell apoptosis and protect against ischemia brain injury via regulation of FOXD3-AS1/miR-765/BCL2L13 axis.
Highlights |
• | Down-regulated FOXD3-AS1 played a neuronal protection role. |
• | FOXD3-AS1 acted as a ceRNA for miR-765, elevating BCL2L13 expression. |
• | FOXD3-AS1 inhibition or miR-765 overexpression could alleviate cell apoptosis |
• | FOXD3-AS1 inhibition or miR-765 overexpression could protect against ischemia brain injury. |
Abstract |
Aims |
Long non-coding RNAs (lncRNAs) FOXD3-AS1 was reported to be increased in cardiomyocyte ischemic injury. However, its role and underlying molecular mechanism in ischemic stroke remain unknown. This study was to investigate the role of FOXD3-AS1 in cerebral ischemia/reperfusion injury.
Methods |
The expression of FOXD3-AS1 and miR-765 were measured with qRT-PCR. The shared putative miR-765 binding sites both in BCL2L13 and FOXD3-AS1 were identified with bioinformatics, luciferase reporter assay and RNA immunoprecipitation. Apoptosis and its related proteins were detected by TUNEL assay, Hoechst 33,258 staining, flow cytometry and western blot. Infarct volume and the neurological status were evaluated with TTC staining and neurologic deficit score, respectively.
Results |
The up-regulation of FOXD3-AS1 and down-regulation of miR-765 were found in both mouse brains after cerebral ischemia/reperfusion (I/R) and neuroblastoma cells of neuro-2A (N2a) after oxygen-glucose deprivation/reoxygenation (OGD/R). Moreover, the overexpression of miR-765 reduced N2a cell apoptosis caused by OGD/R. MiR-765 could target BCL2L13 directly. In addition, we found that FOXD3-AS1 bound to miR-765 directly, acting as a ceRNA to modulate the expression of BCL2L13. Overexpression of FOXD3-AS1 antagonized the inhibitory impact of miR-765 on the expression of BCL2L13 and the apoptosis of N2a cells treated with OGD/R, while FOXD3-AS1 knockdown promoted the inhibitory impact of miR-765 on the expression of BCL2L13 and the apoptosis of N2a cells treated with OGD/R. Furthermore, we found that neurological deficits and brain injury induced by I/R in vivo were attenuated by FOXD3-AS1 knockdown.
Conclusions |
We verified a critical signaling pathway of FOXD3-AS1/miR-765/BCL2L13 in regulating cerebral ischemia/reperfusion injury.
Le texte complet de cet article est disponible en PDF.Keywords : Cerebral ischemia/reperfusion, Apoptosis, FOXD3-AS1, miR-765, BCL2L13
Plan
Vol 132
Article 110778- décembre 2020 Retour au numéro
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