Abstract Purpose MiR-199a-3p is low expressed in diabetic retinopathy (DR). In the current study, we investigated the effects of miR-199a-3p on DR and the potential mechanisms. Methods A DR rat model was established, and endothelial cells (ECs) and retinal pericytes (RPs) were extracted from the DR model rats to detect miR-199a-3p expression. Bioinformatics analysis predicted that fibroblast growth factor 7 (FGF7) was a target gene for miR-199a-3p, which was confirmed by dual-luciferase assay. Cell proliferation, migration, and invasion were detected by cell counting kit-8 (CCK-8), colony formation assay, wound-healing, and Transwell assay. Quantitative real-time polymerase chain reaction (q-PCR) and Western blot were performed to detect the expressions of mRNAs and proteins. Results MiR-199a-3p was low expressed and FGF7 was high-expressed in ECs and RPs. Overexpressed miR-199a-3p suppressed the proliferation, migration, and invasion, and FGF7 expression of ECs and RPs. However, overexpression of FGF7 effectively eliminated the suppressive effects of miR-199a-3p overexpression malignant behaviors of the cells. Meanwhile, up-regulation of FGF7 noticeably reversed the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) and the expression of epidermal growth factor receptor (EGFR) reduced by miR-199a-3p. Conclusion Our findings revealed that in the DR rat model, miR-199a-3p inhibited cell proliferation, migration, and invasion of EC and RP through targeting FGF7 and inhibiting the activation of the EGFR/PI3K/AKT pathway. This study may provide a new direction for the search for the treatment of DR.

中文翻译：

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MiR-199a-3p通过EGFR/PI3K/AKT通路调控FGF7抑制糖尿病视网膜病变大鼠内皮细胞和视网膜周细胞的增殖、迁移和侵袭

摘要目的 MiR-199a-3p 在糖尿病视网膜病变 (DR) 中低表达。在目前的研究中，我们研究了 miR-199a-3p 对 DR 的影响及其潜在机制。方法建立DR大鼠模型，提取DR模型大鼠的内皮细胞（ECs）和视网膜周细胞（RPs），检测miR-199a-3p的表达。生物信息学分析预测成纤维细胞生长因子 7 (FGF7) 是 miR-199a-3p 的靶基因，双荧光素酶测定证实了这一点。通过细胞计数试剂盒8 (CCK-8)、集落形成试验、伤口愈合试验和Transwell试验检测细胞增殖、迁移和侵袭。采用定量实时聚合酶链反应（q-PCR）和蛋白质印迹法检测mRNA和蛋白质的表达。结果 MiR-199a-3p 在 ECs 和 RPs 中低表达，FGF7 高表达。过表达的 miR-199a-3p 抑制了 ECs 和 RPs 的增殖、迁移和侵袭以及 FGF7 的表达。然而，FGF7的过表达有效地消除了miR-199a-3p过表达对细胞恶性行为的抑制作用。同时，FGF7 的上调显着逆转了磷酸肌醇 3-激酶 (PI3K) 和蛋白激酶 B (AKT) 的磷酸化以及 miR-199a-3p 降低的表皮生长因子受体 (EGFR) 的表达。结论 我们的研究结果表明，在 DR 大鼠模型中，miR-199a-3p 通过靶向 FGF7 并抑制 EGFR/PI3K/AKT 通路的激活来抑制 EC 和 RP 的细胞增殖、迁移和侵袭。