ArticleOncogene2020
ISL2 modulates angiogenesis through transcriptional regulation of ANGPT2 to promote cell proliferation and malignant transformation in oligodendroglioma.
Article in Oncogene, 2020. 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, 19 citations in OpenAlex.
- TET2-driven demethylation of ANG promotes angiogenesis and malignant transformation in oligodendroglioma.Oncogene · 2026Article
- From Epigenetic Constraint to Evolutionary Escape: Cell-State Transitions and Selective Pressures During Malignant Transformation in Lower-Grade Gliomas.Biomedicines · 2026Review
- Drug Repurposing for Targeting ISL LIM Homeobox 2 in Treatment of Endometriosis: A Computational Study.International journal of fertility & sterility · 2025Article
- Review
- The evaluation of six genes combined value in glioma diagnosis and prognosis.Journal of cancer research and clinical oncology · 2023Article
- The role of angiogenic growth factors in the immune microenvironment of glioma.Frontiers in oncology · 2023Review
- High LYRM4-AS1 predicts poor prognosis in patients with glioma and correlates with immune infiltration.PeerJ · 2023Article
- HOXB5-activated ANGPT2 promotes the proliferation, migration, invasion and angiogenic effect of esophageal cancer cells via activating ERK/AKT signaling pathway.Experimental and therapeutic medicine · 2022Article
- Ang2-Targeted Combination Therapy for Cancer Treatment.Frontiers in immunology · 2022Review
- Case report: ISL2 is involved in malignant transformation in a patient with multiple relapsed oligodendroglioma.Frontiers in oncology · 2022Article
- A prognostic estimation model based on mRNA-sequence data for patients with oligodendroglioma.Frontiers in neurology · 2022Article
- Activated mesangial cells induce glomerular endothelial cells proliferation in rat anti-Thy-1 nephritis through VEGFA/VEGFR2 and Angpt2/Tie2 pathway.Cell proliferation · 2021Article
- Single-cell transcriptomic analysis of eutopic endometrium and ectopic lesions of adenomyosis.Cell & bioscience · 2021Article
- Development and Validation of an Mesenchymal-Related Long Non-Coding RNA Prognostic Model in Glioma.Frontiers in oncology · 2021Article
- Low expression of developing brain homeobox 2 (Dbx2) may serve as a biomarker to predict poor prognosis in endometrial cancer.American journal of translational research · 2021Article
- Methylation of the Promoter Region of the Tight Junction Protein-1 by DNMT1 Induces EMT-like Features in Multiple Myeloma.Molecular therapy oncolytics · 2020Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oligodendroglioma is an important type of lower-grade glioma (LGG), which is a slowly progressing brain tumor. Many LGGs eventually transform into a more aggressive or malignant type. Enhanced angiogenesis is a characteristic of malignantly transformed oligodendroglioma (m-oligodendroglioma). However, the pathogenesis and signaling pathways associated with angiogenesis and proliferation in m-oligodendroglioma are not well understood. In this study, we identified that Insulin Gene Enhancer Protein (ISL2) and its angiogenic capacity were inversely related to survival according to LGG patient data from an online database, and this was further confirmed with pathological LGG patient samples, including malignantly transformed samples, by detecting the expression of ISL2, the angiogenic markers vascular endothelial growth factor (VEGFA) and CD31 and the proliferation marker Ki-67. We then established novel oligodendroglioma patient tumor-derived orthotopic xenograft mouse models and cell lines to verify the role of ISL2 in regulating angiogenesis to promote oligodendroglioma growth and malignant transformation. Furthermore, ISL2 regulated ANGPT2 transcription by binding to the ANGPT2 promoter. Then, ANGPT2, a downstream gene, activated angiogenesis through VEGFA to promote oligodendroglioma malignant transformation. Finally, combining AAV-ISL2-shRNA with temozolomide suppressed oligodendroglioma progression more effectively than either monotherapy in vivo and in vitro. Thus, hypoxia-induced ISL2 regulated ANGPT2, which subsequently induced angiogenesis to promote oligodendroglioma growth and malignant transformation. Malignancy was accompanied by worsened hypoxia inside the tumor mass, creating a positive feedback loop. In conclusion, this study suggests that ISL2 is a biomarker for oligodendroglioma progression and that anti-ISL2 therapy may offer a potential clinical strategy for treating m-oligodendroglioma.
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