LncRNA SNHG12 inhibits miR-199a to upregulate SIRT1 to attenuate cerebral ischemia/reperfusion injury through activating AMPK signaling pathway
| Autor: | Wei-Lan Yin, Wei-guo Yin, Bai-sheng Huang, Li-xiang Wu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Primary Cell Culture Ischemia Apoptosis AMP-Activated Protein Kinases Hippocampus Mice 03 medical and health sciences 0302 clinical medicine Sirtuin 1 medicine Animals RNA Small Nucleolar RNA Small Interfering Cell Proliferation Neurons Gene knockdown biology Cell growth Chemistry General Neuroscience AMPK medicine.disease Up-Regulation Cell biology MicroRNAs 030104 developmental biology Gene Knockdown Techniques Reperfusion Injury biology.protein RNA Long Noncoding Signal transduction Reperfusion injury 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Neuroscience Letters. 690:188-195 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2018.08.026 |
| Popis: | Cerebral ischemia caused severe disability, and associated with a series of neurological events. Long non-coding RNA SNHG12 was found to be upregulated in mouse brain microvascular endothelial cells by cerebral ischemia. Moreover, it was reported that SNHG12 could directly interact with miR-199a and sirtuin 1 (SIRT1) as a direct target of miR-199a in other diseases. However, the function and mechanism of SNHG12 in cerebral ischemia and reperfusion (I/R) injury of neuronal cells remains unclear. The present study was thus designed to explore the potential effect of SNHG12 and to investigate the underlying mechanism in I/R neuronal cells. we found that SNHG12 was upregulated in primary neuronal cells and N2a cells and peaked at 12 h and 24 h after OGD/R treatment, respectively. Meanwhile, MTT assay showed that knockdown SNHG12 inhibited cell proliferation under OGD/R condition. And flow cytometry analyses revealed more apoptosis rate was caused by SNHG12 knockdown. Mechanistically, SNHG12 interacted with miR-199a and decreased the expression of miR-199a. Overexpression miR-199a largely inhibited the cell proliferation and induced the cell apoptosis. Meanwhile, SNHG12 was proven to target miR-199a and then activated SIRT1 expression, which finally led to activation of AMPK signaling pathway. In summary, we demonstrate SNHG12 targets miR-199a to upregulate SIRT1 expression, which attenuates cerebral ischemia/reperfusion injury through AMPK pathway activation. Our findings provide molecular mechanism by which SNHG12 attenuates cerebral I/R injury and facilitate development of therapeautical strategies for treating ischemia-induced stroke. |
| Databáze: | OpenAIRE |
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