ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
circEHBP1 promotes lymphangiogenesis and lymphatic metastasis of bladder cancer via miR-130a-3p/TGFβR1/VEGF-D signaling.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54 citing papers in PubMed, 82 citations in OpenAlex.
- CCL21/CCR7 axis regulates VEGF-D mHuman cell · 2026Article
- Non-classic deubiquitinase USP13 inhibits bladder cancer metastasis through destabilizing cytoplasmic KDM3A.Oncogene · 2026Article
- Molecular biology of targeting lymphangiogenesis in cancer: Therapeutic strategies and future promise.Fundamental research · 2026Review
- M2 macrophages promote lymphatic metastasis by regulating PKM2 nuclear translocation in triple-negative breast cancer.Cell death & disease · 2026Article
- The involvement of circular RNAs in breast cancer metastasis: Insight into EMT-related signaling pathways.BioImpacts : BI · 2026Review
- Lymphatic Endothelial Cells and Organ-Associated Lymphangiogenesis in Tumor Microenvironment.Cells · 2025Review
- A Liquid Biopsy Assay of Exosomal miRNA for Non-invasive Identification of Lymph Node Metastasis in Early Gastric Cancer.Annals of surgical oncology · 2025Article
- Circular RNAs: Fundamental mechanisms in tumor metastasis and detection strategies (Review).Molecular medicine reports · 2025Review
- The role of circular RNAs in regulating cytokine signaling in cancer.FEBS open bio · 2025Review
- VEGFD/VEGFR2 axis induces the dedifferentiation of high endothelial venules and impairs lymphocyte homing.JCI insight · 2025Article
- Non-classic deubiquitinase USP13 inhibits bladder cancer metastasis through destabilizing cytoplasmic KDM3A.Oncogene · 2025Article
- Treatment of Pathological Lymphangiogenesis via Circular RNA-Mediated Cholesterol Metabolism Remodeling.Investigative ophthalmology & visual science · 2025Article
- Migrasome Marker Epidermal Growth Factor Domain-SpecificBiomedicines · 2025Article
- Small non-coding RNA profiling in patients with non-muscle invasive bladder cancer.BMC cancer · 2025Article
- HOXB7 drives bladder cancer progression via H-Ras/ERK signaling: a potential therapeutic target and prognostic biomarker.Frontiers in oncology · 2025Article
- Epigenetic Biomarkers as a New Diagnostic Tool in Bladder Cancer-From Early Detection to Prognosis.Journal of clinical medicine · 2024Review
- Integrin α6-containing extracellular vesicles promote lymphatic remodelling for pre-metastatic niche formation in lymph nodes via interplay with CD151.Journal of extracellular vesicles · 2024Article
- The role of circular RNA during the urological cancer metastasis: exploring regulatory mechanisms and potential therapeutic targets.Cancer metastasis reviews · 2024Review
- CircRNAs: Pivotal modulators of TGF-β signalling in cancer pathogenesis.Non-coding RNA research · 2024Review
- Uncovering the shared neuro-immune-related regulatory mechanisms between spinal cord injury and osteoarthritis.Heliyon · 2024Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lymphatic metastasis constitutes a leading cause of recurrence and mortality in bladder cancer. Accumulating evidence indicates that lymphangiogenesis is indispensable to trigger lymphatic metastasis. However, the specific mechanism is poorly understood. In the present study, we revealed a pathway involved in lymphatic metastasis of bladder cancer, in which a circular RNA (circRNA) facilitated lymphangiogenesis in a vascular endothelial growth factor C (VEGF-C)-independent manner. Novel circRNA circEHBP1 was markedly upregulated in bladder cancer and correlated positively with lymphatic metastasis and poor prognosis of patients with bladder cancer. circEHBP1 upregulated transforming growth factor beta receptor 1 (TGFBR1) expression through physically binding to miR-130a-3p and antagonizing the suppression effect of miR-130a-3p on the 3' UTR region of TGFBR1. Subsequently, circEHBP1-mediated TGFβR1 overexpression activated the TGF-β/SMAD3 signaling pathway, thereby promoting the secretion of VEGF-D and driving lymphangiogenesis and lymphatic metastasis in bladder cancer. Importantly, administration of VEGF-D neutralizing antibodies remarkably blocked circEHBP1-induced lymphangiogenesis and lymphatic metastasis in vivo. Our findings highlighted that the circEHBP1/miR-130a-3p/TGFβR1/VEGF-D axis contributes to lymphangiogenesis and lymphatic metastasis of bladder cancer independent of VEGF-C, which might lead to the development of circEHBP1 as a potential biomarker and promising therapeutic target for lymphatic metastasis in bladder cancer.
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