Circular RNA Rap1b promotes Hoxa5 histone acetylation by recruiting Kat7 to inhibit neuronal apoptosis in acute ischemic stroke

Abstract Stroke is a common neurological disease and one of the major causes of permanent morbidity and disability worldwide. Although many drugs have shown significant neuroprotective effects in animal models, these results have not been confirmed in human clinical trials. Therefore, search for new treatments is urgent. In human patients and animal stroke models, acute ischemic primary neurons with blocked arterial blood supply die rapidly, while core and surrounding acute ischemic primary neurons that are infused by other arteries undergo delayed apoptosis to some extent. In the present study, we found that circRAP1B was downregulated in patients with acute ischemia stroke (AIS), and it was validated that circRap1b was downregulated in the hippocampus tissues and neurons HT22 cells of C57BL/6J mice treated with acute ischemia-hypoxia (AIS). Moreover, overexpression of circRAap1b inhibited the apoptosis of HT22-AIS cells. We attempted to prove that neuronal apoptosis inhibited by circRap1b/Hoxa5 in vitro might be ascribed to Kat7-induced acetylation of histones H3 Lysine 14 modification in the Hoxa5 promoter region. Promisingly, we hope that circRap1b and Hoxa5 will provide new treatment strategy for stroke.