ArticleDiabetology & metabolic syndrome2021
MiR-423-5p activated by E2F1 promotes neovascularization in diabetic retinopathy by targeting HIPK2.
Article in Diabetology & metabolic syndrome, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- MicroRNAs: A Social Network in Diabetic Retinopathy.Biomolecules · 2026Review
- Endothelial cell-derived microRNAs-containing extracellular vesicles and diabetic retinopathy in a mouse model of diabetes.In vitro cellular & developmental biology. Animal · 2026Article
- Translational insights into miR-126 and miR-423: biomarkers and therapeutic targets in cancer, cardiovascular, metabolic and kidney diseases.Frontiers in molecular biosciences · 2026Review
- LncRNA NR2F1-AS1 is involved in osteogenic differentiation in fracture healing via miR-423-5p.Cytotechnology · 2025Article
- The Role of Non-coding RNAs in Diabetic Retinopathy: Mechanistic Insights and Therapeutic Potential.Molecular neurobiology · 2025Review
- miR-16-5p Regulates Proliferation and Apoptosis in High Glucose-Treated Human Retinal Microvascular Endothelial Cells by Targeting VEGFA and TGFBR1.Journal of ophthalmology · 2025Article
- Human Schwann Cell-Derived Extracellular Vesicle Isolation, Bioactivity Assessment, and Omics Characterization.International journal of nanomedicine · 2025Article
- Article
- Transcriptome analysis and RT-qPCR validation of mitophagy-related key genes in the progression of diabetic retinopathy.Frontiers in endocrinology · 2025Article
- Maternal Salivary miR-423-5p Is Linked to Neonatal Outcomes and Periodontal Status in Cardiovascular-High-Risk Pregnancies.International journal of molecular sciences · 2024Article
- Transcriptome analysis combined with Mendelian randomization screening for biomarkers causally associated with diabetic retinopathy.Frontiers in endocrinology · 2024Article
- MiRNA-423 rs6505162 and miRNA-6811 rs2292879 SNP associated with lung cancer in Hainan, China.Bioscience reports · 2023Article
- The Sweet Side of HIPK2.Cancers · 2023Review
- Elucidating glial responses to products of diabetes-associated systemic dyshomeostasis.Progress in retinal and eye research · 2023Review
- HIPK2 in Angiogenesis: A Promising Biomarker in Cancer Progression and in Angiogenic Diseases.Cancers · 2023Review
- Noncoding RNAs Are Promising Therapeutic Targets for Diabetic Retinopathy: An Updated Review (2017-2022).Biomolecules · 2022Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDiabetic retinopathy (DR) is a diabetic complication and the primary cause of blindness in the world. However, the treatments of DR are challenging given its complicated pathogenesis. Here, we investigated the molecular mechanisms of DR by focusing on the function of E2F1/miR-423-5p/HIPK2/HIF1α/VEGF axis.
methodsCultured retinal endothelial cells (hRMECs, hRECs) were treated with 25 mM glucose to mimic the high glucose-induced DR in vitro. Streptozotocin (STZ) was injected into mice to induce DR in mice. qRT-PCR, western blotting, immunohistochemistry, and ELISA were employed to measure levels of E2F1, miR-423-5p, HIPK2, HIF1α, and VEGF. H&E staining was utilized to examine retinal neovascularization. CCK-8 assay, transwell assay, and vascular tube formation assay were used to assess the cell viability, migration, and angiogenesis. Dual luciferase assay was performed to validate interactions between E2F1 and miR-423-5p, miR-423-5p and HIPK2.
resultsHG treatment increased the cell viability, migration, and angiogenesis accompanied by upregulation of E2F1, miR-423-5p, HIF1α, and VEGF levels, but reduction in HIPK2 expression. Knockdown of E2F1 or miR-423-5p suppressed the HG-induced increases in cell viability, migration, and angiogenesis. E2F1 transcriptionally activated miR-423-5p expression and miR-423-5p mimics blocked the effects of E2F1 knockdown on angiogenesis. Moreover, miR-423-5p directly targeted HIPK2 to disinhibit HIF1α/VEGF signaling. Knockdown of HIPK2 reversed the effects of miR-423-5p inhibitor on cell viability, migration, and angiogenesis. Knockdown of E2F1 suppressed neovascularization during DR in vivo.
conclusionsE2F1 activates miR-423-5p transcription during DR to promote angiogenesis via suppressing HIPK2 expression to disinhibit HIF1α/VEGF signaling. Strategies targeting E2F1/miR-423-5p/HIPK2 axis could be potentially used for DR treatment.
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