This study aimed to explore the molecular regulatory network among microRNA-125b (miR-125b), forkhead box Q1 (FOXQ1), prostaglandin-endoperoxide synthase 2 (PTGS2), and cyclin-dependent kinase 5 (CDK5), as well as their effects on cell apoptosis, neurite outgrowth, and inflammation in Alzheimer disease (AD). Rat embryo cerebral cortex neurons and nerve growth factor–stimulated PC12 cells were insulted by Aβ₁₋₄₂ to construct two AD cellular models. Negative control (NC) inhibitor, miR-125b inhibitor, NC siRNA, FOXQ1 siRNA, PTGS2 siRNA, and CDK5 siRNA were transferred into the two AD cellular models alone or combined. Then, cell apoptosis, neurite outgrowth, proinflammatory cytokines, miR-125b, FOXQ1, PTGS2, and CDK5 expressions were detected. MiR-125b inhibition facilitated neurite outgrowth but suppressed cell apoptosis and proinflammatory cytokines (tumor necrosis factor-α, interleukin 1β, and interleukin 6); meanwhile, it upregulated FOXQ1 but downregulated PTGS2 and CDK5. Furthermore, FOXQ1 inhibition promoted cell apoptosis and proinflammatory cytokines but repressed neurite outgrowth; PTGS2 inhibition achieved the opposite effects; CDK5 inhibition attenuated cell apoptosis, whereas it less affected neurite outgrowth and inflammation. Notably, FOXQ1 inhibition attenuated, whereas PTGS2 inhibition elevated the effect of miR-125b inhibition on regulating neurite outgrowth, cell apoptosis, and proinflammatory cytokines. As for CDK5 inhibition, it enhanced the effect of miR-125b inhibition on regulating cell apoptosis, but less impacted the neurite outgrowth and proinflammatory cytokines. Additionally, PTGS2 inhibition and CDK5 inhibition both reversed the effect of FOXQ1 inhibition on regulating cell apoptosis, neurite outgrowth, and proinflammatory cytokines. In conclusion, targeting miR-125b alleviates AD progression via blocking PTGS2 and CDK5 in a FOXQ1-dependent way.

这项研究旨在探讨microRNA-125b（miR-125b），叉头盒Q1（FOXQ1），前列腺素内过氧化物合酶2（PTGS2）和细胞周期蛋白依赖性激酶5（CDK5）之间的分子调控网络，以及它们的作用。对阿尔茨海默病（AD）中细胞凋亡，神经突生长和炎症的影响。大鼠胚胎大脑皮质神经元和神经生长因子刺激的PC12细胞受到_{Aβ1-42的侵害}来构建两个AD细胞模型。阴性对照（NC）抑制剂，miR-125b抑制剂，NC siRNA，FOXQ1 siRNA，PTGS2 siRNA和CDK5 siRNA单独或合并转移到两个AD细胞模型中。然后，检测细胞凋亡，神经突增生，促炎细胞因子，miR-125b，FOXQ1，PTGS2和CDK5表达。MiR-125b抑制促进神经突生长，但抑制细胞凋亡和促炎细胞因子（肿瘤坏死因子-α，白介素1β和白介素6）；同时，它上调了FOXQ1，但下调了PTGS2和CDK5。此外，FOXQ1抑制促进细胞凋亡和促炎细胞因子，但抑制神经突生长。PTGS2的抑制作用相反。CDK5抑制可减弱细胞凋亡，而对神经突生长和炎症影响较小。值得注意的是 FOXQ1抑制减弱，而PTGS2抑制增强了miR-125b抑制对调节神经突生长，细胞凋亡和促炎细胞因子的作用。至于CDK5抑制，它增强了miR-125b抑制对调节细胞凋亡的作用，但对神经突生长和促炎细胞因子的影响较小。此外，PTGS2抑制和CDK5抑制均逆转了FOXQ1抑制对调节细胞凋亡，神经突增生和促炎细胞因子的作用。总之，靶向miR-125b通过以FOXQ1依赖的方式阻断PTGS2和CDK5来缓解AD进展。它增强了miR-125b抑制作用对细胞凋亡的调节作用，但对神经突生长和促炎细胞因子的影响较小。此外，PTGS2抑制和CDK5抑制均逆转了FOXQ1抑制对调节细胞凋亡，神经突增生和促炎细胞因子的作用。总之，靶向miR-125b通过以FOXQ1依赖的方式阻断PTGS2和CDK5来缓解AD进展。它增强了miR-125b抑制作用对细胞凋亡的调节作用，但对神经突生长和促炎细胞因子的影响较小。此外，PTGS2抑制和CDK5抑制均逆转了FOXQ1抑制对调节细胞凋亡，神经突增生和促炎细胞因子的作用。总之，靶向miR-125b通过以FOXQ1依赖的方式阻断PTGS2和CDK5来缓解AD进展。