Objective: Our previous study observed that circular RNA AXL (circ-AXL, access number circ_0002945) was closely correlated with disease risk and severity of Alzheimer's Disease (AD) by microarray and RT-qPCR validation. Then this current study aimed to further investigate the effect of circ-AXL on regulating neuron injury and inflammation in cellular AD models and its underlying molecular mechanism.
Methods: SK-N-SH and SK-SY5Y cell lines were treated by amyloid β to construct cellular AD models. Then control or circ-AXL overexpression, control or circ-AXL knock-down, microRNA-328 (miR-328) knock-down with or without circ-AXL knock-down, as well as BACE1 overexpression with or without miR-328 overexpression plasmids were transfected into cellular AD models. Furthermore, neuron injury and inflammation were detected.
Results: Circ-AXL overexpression increased apoptosis rate and declined neurite outgrowth, as well as elevated inflammatory cytokines in cellular AD models; but circ-AXL knockdown exhibited opposite effects. Additionally, circ-AXL negatively regulated miR-328 but positively modulated BACE1; besides, miR-328 negatively regulated BACE1; further luciferase reporter gene assay presented that circ-AXL directly bound miR-328, and miR-328 directly bound BACE1. Furthermore, miR-328 overexpression decreased apoptosis rate, elevated neurite outgrowth, and declined inflammatory cytokines in cellular AD models; but miR-328 knockdown presented opposite effects. Notably, miR-328 knockdown attenuated the effect of circ-AXL knockdown on cellular AD models. Moreover, BACE1 overexpression aggravated neuron injury and inflammation, as well as attenuated the effect of miR-328 overexpression on these functions in cellular AD models.
Conclusion: Circ-AXL may serve as a potential treatment target via miR-328 mediated BACE1 in AD.
Keywords: Alzheimer’s disease; BACE1; Circular RNA AXL; Neuron injury and inflammation; microRNA-328.
Copyright © 2022. Published by Elsevier B.V.