MiR-99a-5p Inhibits the Proliferation and Migration of Human Retinal Microvascular Endothelial Cells by Targeting NOX4

Abstract

Diabetic retinopathy is one of the common microvascular complications of diabetes, and it is the main cause of vision loss among working-age people. This study interpreted the roles of miR-99a-5p in DR patients and human retinal microvascular endothelial cell (hRMECs) injury induced by high glucose. The expression of miR-99a-5p was detected in patients with NDR, NPDR, and PDR. The indictive impacts of miR-99a-5p were tested by the ROC curve, and the link between miR-99a-5p and clinical information was verified by the Pearson test. HG was used to instruct cell models. The CCK-8 and transwell methods were performed to detect the proliferative and migrated cells. The targeted relationship was explained by luciferase activity. The content of miR-99a-5p was gradually lessened in NPDR and PDR patients. MiR-99a-5p might differentiate DR patients from NDR patients and PDR patients from NPDR patients. The interconnection between miR-99a-5p and clinical factors was endorsed in all DR patients. Overexpression of miR-99a-5p assuaged the abnormality of cell migration and proliferation of hRMECs triggered by HG. NOX4 was a downstream signaling component of miR-99a-5p. In conclusion, MiR-99a-5p protected hRMECs against HG damage, and the miR-99a-5p might be a novel target for diagnosis of DR.

Nox4 as a novel therapeutic target for diabetic vascular complications

“…Additionally, overexpression of miR-99a-5p mitigated the deleterious effects of high glucose on HRMECs' proliferation. Nox4 was identified as a downstream target of miR-99a-5p, and its upregulation triggered by high glucose was decreased by miR-99a-5p overexpression [ 137 ]. In summary, miR-99a-5p improves DR by inhibiting the abnormal proliferation and migration of human retinal microvascular endothelial cells through targeting Nox4.…”

“…In contrast, overexpression of miR-99a-5p mitigated the deleterious effects of HG. [ 137 ] Diabetic cardiomyopathy miR-372-3p miR-372-3p KD treatment raised expression of p-PI3K, p-AKT, p-mTOR, p-P70S6K and HIF-1α, while downregulating Nox2, and Nox4 expression. In addition, LVFS and LVEF were increased, LVIDd and LVIDs were decreased.…”