ArticleMolecular cancer2023
Extracellular vesicle-circEHD2 promotes the progression of renal cell carcinoma by activating cancer-associated fibroblasts.
Article in Molecular cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 48 citations in OpenAlex.
- Circular RNAs in tumorigenesis: an insight into recent research in biogenesis and targeted tumor therapy.Cell cycle (Georgetown, Tex.) · 2026Review
- Exosomal circular RNAs in the tumor immune microenvironment: From regulatory mechanisms to therapeutic opportunities and translational hurdles (Review).International journal of molecular medicine · 2026Review
- Extracellular Vesicles: Classification, Biological Functions, Diseases, and Therapeutic Opportunities.MedComm · 2026Review
- Extracellular Vesicles in Cancer: Biomarkers, Mechanisms, and Emerging Diagnostic Technologies.Advanced healthcare materials · 2026Review
- Cardiac-derived extracellular vesicles carrying miR-4433b-3p accelerate cognitive decline and brain aging by suppressing TP53INP2-mediated neuronal autophagy in mice.Communications biology · 2026Article
- Cargo-driven extracellular vesicles as pharmaceutical nanocarriers: A pharmaceutics-oriented comparison of animal exosomes and plant-derived exosome-like nanoparticles.International journal of pharmaceutics: X · 2026Review
- CircRPPH1 promotes hepatocellular carcinoma progression through inhibiting PPARα transcription and accelerating its ubiquitination and degradation.Cellular and molecular life sciences : CMLS · 2026Article
- Unveiling the epigenetic landscape: transforming renal cell carcinoma treatment.Clinical epigenetics · 2026Review
- Tumor exosomes impact functional hallmarks of cancer.Cancer metastasis reviews · 2026Review
- Review
- CircCCDC66 promotes the progression and EMT of renal cell carcinoma via the miR-1278/HOXA13 axis.Journal of translational medicine · 2026Article
- Metabolic Messengers: Extracellular Vesicles as Central Mediators of Metabolic Reprogramming in Renal Cell Cancer.Biomedicines · 2026Review
- HNRNPA2B1 as an emerging coordinator of RNA fate in cancer: m6A reading, RNA export, translation reprogramming, and immune-metabolic adaptation.Frontiers in immunology · 2026Review
- Silencing of circRERE(4-5) inhibits ONECUT2-mediated tumorigenesis and metastasis in gastric cancer.Frontiers in immunology · 2026Article
- Extracellular vesicles as modulators of cancer metabolism and microenvironment.Extracellular vesicles and circulating nucleic acids · 2026Review
- Deciphering the mechanistic landscape of immune checkpoint blockade in ccRCC: from molecular drivers to therapeutic responses.Frontiers in immunology · 2026Review
- Circular RNA circEVI5 functions as a miR-433 sponge to promote renal cell carcinoma progression via GBP2-mediated oncogenic signaling.Frontiers in oncology · 2026Article
- The value of dual-energy CT radiomics in evaluating vascular maturity and prognosis in clear cell renal cell carcinoma.Discover oncology · 2025Article
- Cancer-associated fibroblast-derived extracellular vesicles facilitate metastasis in hepatocellular carcinoma by delivering CTGF.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- m6A modification of non‑coding RNA: Mechanisms, functions and potential values in human diseases (Review).International journal of molecular medicine · 2025Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe encapsulation of circular RNAs (circRNAs) into extracellular vesicles (EVs) enables their involvement in intercellular communication and exerts an influence on the malignant advancement of various tumors. However, the regulatory role of EVs-circRNA in renal cell carcinoma (RCC) remains elusive.
methodsThe in vitro and in vivo functional experiments were implemented to measure the effects of circEHD2 on the phenotype of RCC. The functional role of EVs-circEHD2 on the activation of fibroblasts was assessed by collagen contraction assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). The mechanism was investigated by RNA pull-down assay, RNA immunoprecipitation, chromatin isolation by RNA purification, luciferase assay, and co-immunoprecipitation assay.
resultsWe demonstrated that circEHD2 was upregulated in RCC tissues and serum EVs of RCC patients with metastasis. Silencing circEHD2 inhibited tumor growth in vitro and in vivo. Mechanistic studies indicated that FUS RNA -binding protein (FUS) accelerated the cyclization of circEHD2, then circEHD2 interacts with tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH), which acts as a bridge to recruit circEHD2 and Yes1-associated transcriptional regulator (YAP) to the promoter of SRY-box transcription factor 9 (SOX9); this results in the sustained activation of SOX9. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) regulates the package of circEHD2 into EVs, then EVs-circEHD2 transmits to fibroblasts, converting fibroblasts to cancer-associated fibroblasts (CAFs). Activated CAFs promote the metastasis of RCC by secreting pro-inflammatory cytokines such as IL-6. Furthermore, antisense oligonucleotides (ASOs) targeting circEHD2 exhibited a strong inhibition of tumor growth in vivo.
conclusionsThe circEHD2/YWHAH/YAP/SOX9 signaling pathway accelerates the growth of RCC. EVs-circEHD2 facilitates the metastasis of RCC by converting fibroblasts to CAFs. Our results suggest that EVs-circEHD2 may be a useful biomarker and therapeutic target for RCC.
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