Abstract
One important feature of cerebral ischemia is hypoxia injury in nerve cells. Growth arrest-specific transcript 5 (GAS5) is widely reported as a tumor suppressor gene; however, the investigations about its role in cerebrovascular disease are relatively rare. This study was aimed to explore the impact of GAS5 on hypoxia response in nervous cells. PC-12 cells were incubated under anoxic condition to induce hypoxia injury. Regulatory effects of GAS5 on miR-124 and miR-124 on ICAM-1 expression were assessed by qRT-PCR and/or Western blot. Targeting effect of miR-124 on ICAM-1 3'-untranslated regions (UTR) was evaluated through dual luciferase activity assay. The potential regulatory mechanism on hypoxia injury in PC-12 cells was assessed by detecting key elements of NF-κB and Notch signaling pathways using Western blot. GAS5 ectopic expression accentuated hypoxia injury in PC-12 cells. miR-124 expression was negatively regulated by GAS5 expression. Cells with overexpressions of GAS5 and miR-124 alleviated hypoxia injury as in compassion with cells only with GAS5 overexpression. ICAM-1 expression was negatively regulated by miR-124 expression. ICAM-1 was a functional target of miR-124. ICAM-1 overexpression aggravated hypoxia injury, but inversely, ICAM-1 silence diminished hypoxia damage. Besides, ICAM-1 expression was negatively related with activation of NF-κB and Notch pathways. GAS5-miR-124-ICAM-1 axis could regulate hypoxia injury in PC-12 cells. GAS5 might aggravate hypoxia injury via down-regulating miR-124, then up-regulating ICAM-1, and further enhancing activations of NF-κB and Notch pathways.