Annals of clinical and laboratory science · 2023
LncRNA PCBP1-AS1 Induces Cerebral Ischemia/Reperfusion Injury via the miR-506-3p/CCL2 Axis.
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He Zhili, Chen Ling, Zhang Wei
Аннотация
OBJECTIVE: Long non-coding RNAs (lncRNAs) have been demonstrated to play important roles in ischemic stroke. In this study, we investigated the roles and action mechanism of lncRNA poly(rC)-binding protein 1-antisense RNA 1 (PCBP1-AS1) in cerebral ischemia/reperfusion (I/R) injury.
METHODS: We used a middle cerebral artery occlusion (MCAO) model in vivo and an oxygen-glucose deprivation/reperfusion (OGDR) model in vitro to investigate the mechanism of I/R injury. Cell counting kit-8 assay was used to assess the cell viability, and the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling and western blotting assays were used to evaluate the apoptosis of cells. We also determined the middle cerebral artery occlusion (MCAO)-induced infarct size in vivo using 2, 3, 5-triphenyltetrazolium chloride staining. The predicted targeted regulatory relationships of miR-506-3p with lncRNA PCBP1-AS1 and CCL2 were evaluated via luciferase reporter assays.
RESULTS: We found that lncRNA PCBP1-AS1 and C-C motif chemokine ligand 2 (CCL2) levels were upregulated in OGDR-induced SH-SY 5Y cells and the MCAO rat model. Moreover, silencing of lncRNA PCBP1-AS1 improved the viability and attenuated the apoptosis of OGDR-induced SH-SY 5Y cells. LncRNA PCBP1-AS1 silencing partially recovered the infarct size and suppressed the apoptosis in the MCAO model in vivo. Mechanistically, lncRNA PCBP1-AS1 targeted microRNA (miR)-506-3p, which recognized the CCL2 3'-untranslated region. Notably, CCL2 overexpression abrogated the inhibitory effect of lncRNA PCBP1-AS1 silencing on OGDR-induced cell growth.
CONCLUSION: LncRNA PCBP1-AS1 sequesters miR-506-3p to upregulate CCL2 expression, thereby aggravating I/R injury, suggesting its potential for RNA-targeted treatment of cerebral ischemic stroke.
METHODS: We used a middle cerebral artery occlusion (MCAO) model in vivo and an oxygen-glucose deprivation/reperfusion (OGDR) model in vitro to investigate the mechanism of I/R injury. Cell counting kit-8 assay was used to assess the cell viability, and the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling and western blotting assays were used to evaluate the apoptosis of cells. We also determined the middle cerebral artery occlusion (MCAO)-induced infarct size in vivo using 2, 3, 5-triphenyltetrazolium chloride staining. The predicted targeted regulatory relationships of miR-506-3p with lncRNA PCBP1-AS1 and CCL2 were evaluated via luciferase reporter assays.
RESULTS: We found that lncRNA PCBP1-AS1 and C-C motif chemokine ligand 2 (CCL2) levels were upregulated in OGDR-induced SH-SY 5Y cells and the MCAO rat model. Moreover, silencing of lncRNA PCBP1-AS1 improved the viability and attenuated the apoptosis of OGDR-induced SH-SY 5Y cells. LncRNA PCBP1-AS1 silencing partially recovered the infarct size and suppressed the apoptosis in the MCAO model in vivo. Mechanistically, lncRNA PCBP1-AS1 targeted microRNA (miR)-506-3p, which recognized the CCL2 3'-untranslated region. Notably, CCL2 overexpression abrogated the inhibitory effect of lncRNA PCBP1-AS1 silencing on OGDR-induced cell growth.
CONCLUSION: LncRNA PCBP1-AS1 sequesters miR-506-3p to upregulate CCL2 expression, thereby aggravating I/R injury, suggesting its potential for RNA-targeted treatment of cerebral ischemic stroke.