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- Title
Up‐regulation of miR‐192‐5p inhibits the ELAVL1/PI3Kδ axis and attenuates microvascular endothelial cell proliferation, migration and angiogenesis in diabetic retinopathy.
- Authors
Fu, Xiao‐Lin; He, Fu‐Tao; Li, Mo‐Han; Fu, Chun‐Yan; Chen, Jian‐Zhi
- Abstract
Background: Diabetic retinopathy (DR) is a common complication of diabetes mellitus that poses a threat to adults. MicroRNAs (miRNAs) play a key role in DR progression. However, the role and mechanism of miR‐192‐5p in DR remain unclear. We aimed to investigate the effect of miR‐192‐5p on cell proliferation, migration and angiogenesis in DR. Methods: Expression of miR‐192‐5p, ELAV‐like RNA binding protein 1 (ELAVL1) and phosphoinositide 3‐kinase delta (PI3Kδ) in human retinal fibrovascular membrane (FVM) samples and human retinal microvascular endothelial cells (HRMECs) was assessed using RT‐qPCR. ELAVL1 and PI3Kδ protein levels were evaluated by Western blot. RIP and dual luciferase reporter assays were performed to confirm the miR‐192‐5p/ELAVL1/PI3Kδ regulatory networks. Cell proliferation, migration and angiogenesis were assessed by CCK8, transwell and tube formation assays. Results: MiR‐192‐5p was decreased in FVM samples from DR patients and high glucose (HG)‐treated HRMECs. Functionally, overexpressed miR‐192‐5p inhibited cell proliferation, migration and angiogenesis in HG‐treated HRMECs. Mechanically, miR‐192‐5p directly targeted ELAVL1 and decreased its expression. We further verified that ELAVL1 bound to PI3Kδ and maintained PI3Kδ mRNA stability. Rescue analysis demonstrated that the suppressive effects of HG‐treated HRMECs caused by miR‐192‐5p up‐regulation were overturned by overexpressed ELAVL1 or PI3Kδ. Conclusion: MiR‐192‐5p attenuates DR progression by targeting ELAVL1 and reducing PI3Kδ expression, suggesting a biomarker for the treatment of DR.
- Subjects
ENDOTHELIAL cells; ANALYSIS of variance; NEOVASCULARIZATION; MICRORNA; CELL motility; CELL survival; T-test (Statistics); CELL proliferation; RESEARCH funding; DESCRIPTIVE statistics; REPEATED measures design; GENE expression profiling; DIABETIC retinopathy; BIOLOGICAL assay; DATA analysis software
- Publication
Diabetic Medicine, 2023, Vol 40, Issue 9, p1
- ISSN
0742-3071
- Publication type
Article
- DOI
10.1111/dme.15077