AAV2.7m8-Mediated MicroRNA Expression Suppresses VEGF-Induced Angiogenic Responses in HUVEC
Open accessAbstract
Vascular endothelial growth factor (VEGF)-driven pathological angiogenesis constitutes a primary driver of neovascular diseases, including neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR). Although anti-VEGF agents demonstrate clinical efficacy, their limited intraocular half-life mandates repeated intravitreal injections, thereby highlighting the imperative for long-term therapeutic strategies. In the present study, we assessed the anti-angiogenic potential of retinal organoid-derived microRNAs (miRNA) delivered via an engineered adeno-associated virus vector. Human umbilical vein endothelial cells (HUVEC) were transduced with AAV2.7m8 vectors to overexpress three candidate miRNA (miR-26a, miR-122, and let-7a), followed by VEGF stimulation to evaluate downstream signaling pathways and angiogenic responses. AAV2.7m8-mediated transduction of HUVEC demonstrated high efficiency without inducing detectable cytotoxicity. Overexpression of these miRNA markedly attenuated VEGF-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. Functional assays demonstrated suppression of endothelial cell proliferation and cell cycle progression, with miR-122-5p additionally inhibiting migration. All three miRNA substantially inhibited capillary-like tube formation. In aggregate, these results affirm that AAV2.7m8-mediated delivery of retinal organoid-derived miRNA -namely miR-26a-5p, miR-122-5p, and let-7a-5p-markedly suppresses VEGF-induced angiogenic signaling cascades and endothelial cell activation in vitro, thereby establishing their viability as a sustained therapeutic approach for pathological retinal neovascularization.
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The three selected miRNAs-hsa-miR-122-5p, hsa-let-7a-5p, and hsa-miR-26a-5p-provide complementary and comprehensive coverage of almost all critical genes associated with the MAPK signaling pathway.
“From this analysis, we selected the three abundant miRNAs-hsa-miR-122-5p, hsa-let-7a-5p, and hsa-miR26a-5p-based on their complementary and comprehensive coverage of almost all the critical genes associated with the MAPK signaling pathway 27-33 as analyzed using miRTarBase version 8.0 and TarBase v8.0 integrated within miRNet (Figure S1).”
From rAAV-mediated Multi-miRNA Delivery Targeting MAPK Pathway Suppresses Laser-induced Choroidal Neovascularization in Mice (2026) · cites this paper as [28]
The Results (§2.1) and Discussion (§3.4; page numbers unavailable) associate the three miRNAs’ target genes with kinase-mediated and MAPK signaling. They do not establish complementary coverage of almost all critical MAPK genes. The Methods (§4.4) describe analysis using miRTarBase Release 10.0 and Enrichr, not the cited miRNet-based analysis. (LLM, conf=0.86)
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Self-citation
- Authors
- Yang, J. Y., Choi, J.-S., & Park, T. K.
- Affiliations
- Soonchunhyang University Hospital Bucheon (KR)
- Corresponding author
- Park, Tae Kwann
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2026-03-30
- Volume
- 27
- Issue
- 7
- Pages
- 3123
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC13072725
- OpenAlex
- W7143532918
- Cited by
- 1
- References
- 49
- Citations by year
- 2026: 1
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Bio & Medical Technology Development Program (RS-2025–02217948)
- Basic Science Research Program (RS-2024-00452984)
- Korean government
- Soonchunhyang University https://ror.org/03qjsrb10
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- microRNA delivery, VEGF-induced angiogenesis, neovascular age-related macular degeneration, diabetic retinopathy, retinal organoids, miR-26a-5p, miR-122-5p, let-7a-5p, MAPK signaling, endothelial cell proliferation, endothelial cell migration, capillary tube formation, anti-angiogenic therapy
- MeSH terms
- Angiogenesis, Dependovirus, Cell Movement, Genetic Vectors, Humans, Neovascularization, Pathologic, Signal Transduction, Neovascularization, Physiologic, MicroRNAs, Vascular Endothelial Growth Factor A, Cell Proliferation, Human Umbilical Vein Endothelial Cells
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