ArticleJournal of experimental & clinical cancer research : CR2023
Targeting tumor exosomal circular RNA cSERPINE2 suppresses breast cancer progression by modulating MALT1-NF-𝜅B-IL-6 axis of tumor-associated macrophages.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 84 citations in OpenAlex.
- Exosomal circular RNAs in the tumor immune microenvironment: From regulatory mechanisms to therapeutic opportunities and translational hurdles (Review).International journal of molecular medicine · 2026Review
- Role of circular RNAs in regulating toxicity induced by cancer therapies.Genes & diseases · 2026Review
- Exosomal circ_0050688 Shapes a Chemoresistant Microenvironment by Driving Spatial Resistance Spreading in Glioblastoma via the MDM2 Pathway.Biomolecules · 2026Article
- A novel peptide MIB1-223aa encoded by exosomal circMIB1 from cancer-associated fibroblasts drives triple-negative breast cancer metastasis and stemness via stabilizing MIB1 to activate Notch signaling.Journal of advanced research · 2026Article
- Alternative splicing in cancer drug resistance: Mechanisms and therapeutic prospects (Review).Oncology reports · 2026Review
- Emerging clinical applications of exosomes in breast cancer management from biomarkers to therapeutics.Discover oncology · 2026Review
- Exosomal crosstalk between breast cancer cells and tumor-associated macrophages: mechanisms and therapeutic implications.Molecular biology reports · 2026Review
- Circular RNAs in tumor immunity and immunotherapy of breast cancer.Frontiers in immunology · 2026Review
- Preclinical Nanoparticle Approaches Targeting Tumor-Associated Macrophages in Breast Cancer: From Mechanisms to Therapeutic Strategies.International journal of nanomedicine · 2026Review
- Article
- CircRNA-mediated regulation of immune checkpoints in lymphoma: a multidimensional network perspective.Frontiers in immunology · 2026Review
- Fucosyltransferase 8-Derived Circular RNA Drives M2 Polarization of Macrophages Through ENO1-TNF Signaling Axis to Promote Lung Cancer Progression.Thoracic cancer · 2025Article
- Microenvironmental regulation and remodeling of breast cancer angiogenesis: from basic mechanisms to clinical therapeutic implications.Discover oncology · 2025Review
- Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review).International journal of oncology · 2025Review
- The role of circular RNAs in regulating cytokine signaling in cancer.FEBS open bio · 2025Review
- Regulatory roles of circular RNAs in Wnt and other oncogenic signaling pathways in breast cancer progression: a comprehensive review.European journal of medical research · 2025Review
- Blood MALT1 expression levels reflect the lymph node stage and disease-free survival in patients with non-small cell lung cancer.Oncology letters · 2025Article
- Review
- PLGA microspheres loaded with si-circETS1 as a therapeutic strategy to delay intervertebral disc degeneration.Cytotechnology · 2025Article
- Developmental Regulation of circRNAs in Normal and Diseased Mammary Gland: A Focus on circRNA-miRNA Networks.Journal of mammary gland biology and neoplasia · 2025Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCircular RNAs (circRNAs) have important regulatory functions in cancer, but the role of circRNAs in the tumor microenvironment (TME) remains unclear. Moreover, we also explore the effects of si-circRNAs loaded in nanoparticles as therapeutic agent for anti-tumor in vivo.
methodsWe conducted bioinformatics analysis, qRT-PCR, EdU assays, Transwell assays, co-culture system and multiple orthotopic xenograft models to investigate the expression and function of circRNAs. Additionally, PLGA-based nanoparticles loaded with si-circRNAs were used to evaluate the potential of nanotherapeutic strategy in anti-tumor response.
resultsWe identified oncogene SERPINE2 derived circRNA, named as cSERPINE2, which was notably elevated in breast cancer and was closely related to poor clinical outcome. Functionally, tumor exosomal cSERPINE2 was shuttled to tumor associated macrophages (TAMs) and enhanced the secretion of Interleukin-6 (IL-6), leading to increased proliferation and invasion of breast cancer cells. Furthermore, IL-6 in turn increased the EIF4A3 and CCL2 levels within tumor cells in a positive feedback mechanism, further enhancing tumor cSERPINE2 biogenesis and promoting the recruitment of TAMs. More importantly, we developed a PLGA-based nanoparticle loaded with si-cSERPINE2, which effectively attenuated breast cancer progression in vivo.
conclusionsOur study illustrates a novel mechanism that tumor exosomal cSERPINE2 mediates a positive feedback loop between tumor cells and TAMs to promote cancer progression, which may serve as a promising nanotherapeutic strategy for the treatment of breast cancer.
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