In the current study, we aimed to study the effect of miR-146a on proliferation and migration in an in vitro diabetic foot ulcer (DFU) model by targeting A-kinase-anchoring protein 12 (AKAP12). An in vitro DFU model was initially established using HaCaT cells derived from human keratinocytes and induced by advanced glycation end products (AGEs). The effects of overexpression of miR-146a on proliferation and migration ability were analysed. The expression levels of miR-146a and AKAP12 were measured by quantitative real-time polymerase chain reaction (qRT-PCR), and AKAP12, hypoxia-inducible factor-1α (HIF-1α), Wnt3a and β-catenin protein levels were measured by western blotting. The cell proliferation ability was measured by MTT, and the migration ability was analysed by a cell scratch assay. The binding between miR-146a and AKAP12 was identified using a luciferase reporter assay. The results demonstrated that AGEs significantly suppressed cell proliferation and migration, while the expression of miR-146a decreased and the expression of AKAP12 increased. A luciferase reporter assay revealed that miR-146a could directly target AKAP12. Overexpression of miR-146a promoted cell proliferation and migration in an in vitro DFU model and also promoted the expression of HIF-1α, Wnt3a and β-catenin but suppressed the expression of AKAP12. Co-overexpression of miR-146a and AKAP12 reversed the effect of miR-146a on cell proliferation and migration. Our findings revealed that miR-146a directly targeted AKAP12 and promoted cell proliferation and migration in an in vitro DFU model. This study provides a new perspective for the study of miR-146a in the treatment of DFU.

在目前的研究中，我们旨在通过靶向 A-激酶锚定蛋白 12 (AKAP12)来研究 miR-146a 对体外糖尿病足溃疡 (DFU) 模型中增殖和迁移的影响。体外_DFU 模型最初是使用源自人类角质形成细胞并由晚期糖基化终产物 (AGEs) 诱导的 HaCaT 细胞建立的。分析了过表达miR-146a对增殖和迁移能力的影响。miR-146a 和 AKAP12 的表达水平通过定量实时聚合酶链反应 (qRT-PCR) 测量，AKAP12、缺氧诱导因子 1α (HIF-1α)、Wnt3a 和 β-catenin 蛋白水平通过蛋白质印迹法。MTT法测定细胞增殖能力，细胞划痕法分析迁移能力。使用荧光素酶报告基因测定鉴定了 miR-146a 和 AKAP12 之间的结合。结果表明，AGEs显着抑制细胞增殖和迁移，而miR-146a的表达降低，AKAP12的表达增加。荧光素酶报告基因分析显示 miR-146a 可以直接靶向AKAP12。在体外DFU 模型中，miR-146a 的过表达促进了细胞增殖和迁移，也促进了 HIF-1α、Wnt3a 和 β-catenin 的表达，但抑制了 AKAP12 的表达。miR-146a 和AKAP12的共过表达逆转了 miR-146a 对细胞增殖和迁移的影响。我们的研究结果表明，在体外DFU 模型中，miR-146a 直接靶向AKAP12并促进细胞增殖和迁移。本研究为研究miR-146a治疗DF​​U提供了新的视角。