Long non-coding RNA TTTY15 sponges miR-520a-3p to exacerbate neural apoptosis induced by cerebral ischemia/reperfusion via targeting IRF9 both in vivo and in vitro

Autor: Huan Wang, Hui Yang, Mingxiu Chang, Feifei Sun, Huiping Qi, Xuling Li
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Biomedical Journal, Vol 46, Iss 2, Pp 100530- (2023)
Druh dokumentu: article
ISSN: 2319-4170
DOI: 10.1016/j.bj.2022.04.001
Popis: Background: Studies have proven that as competing endogenous RNAs (ceRNAs), long non-coding RNAs (lncRNAs) play vital roles in regulating RNA transcripts in ischemic stroke. It has been reported that TTTY15, a lncRNA, is dysregulated in cardiomyocytes after ischemic injury. We intended to explore the potential regulating mechanism of TTTY15 in ischemic stroke. Methods: TTTY15 and miR-520a-3p levels in vivo were measured in the cerebral ischemia/reperfusion (I/R) model. Cell apoptosis was measured by flow cytometry. To manifest TTTY15 functions in I/R injury, Neuro 2a (N2a) cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) and treated with si-NC, pcDNA3.1-NC, si-TTTY15 or pcDNA3.1-TTTY15. Results: TTTY15 expression was elevated and miR-520a-3p expression was declined in mouse brains exposed to I/R and in N2a cells exposed to OGD/R. Bioinformatics analyses predicted the binding sites of miR-520a-3p in the 3′-UTRs of interferon regulatory factor 9 (IRF9) and TTTY15. Luciferase reporter assay exhibited that TTTY15 bound to miR-520a-3p directly and IRF9 was targeted by miR-520a-3p. MiR-520a-3p overexpression diminished N2a cell apoptosis caused by OGD/R. TTTY15 overexpression antagonized the inhibitory impacts of miR-520a-3p on IRF9 expression and apoptosis after OGD/R, while TTTY15 knockdown enhanced the inhibitory impacts of miR-520a-3p. Additionally, TTTY15 knockdown alleviated brain damages and neurological deficits induced by I/R in vivo. Our results revealed that TTTY15 modulated IRF9 via acting as a ceRNA for miR-520a-3p. Conclusion: The study revealed the roles of TTTY15/miR-520a-3p/IRF9 signaling pathway in regulating cerebral ischemia/reperfusion injury.
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