ArticleJournal of experimental & clinical cancer research : CR2021
Hypoxic tumour cell-derived exosomal miR-340-5p promotes radioresistance of oesophageal squamous cell carcinoma via KLF10.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 114 citations in OpenAlex.
- Review
- Metformin in gastrointestinal cancers and inflammatory bowel disease: Unraveling its mechanisms and therapeutic applications.iScience · 2026Review
- The avatar principle: exosomal dynamics guiding tumor adaptation and next-generation therapeutic strategies.Journal of nanobiotechnology · 2026Review
- Convergent adaptive architectures linking chemoresistance and radioresistance in chemoradiotherapy: a systems-level perspective.Frontiers in oncology · 2026Review
- Radiation-induced extracellular vesicles from cancer-associated fibroblasts drive oesophageal squamous cell carcinoma metastasis via the miR-193a-3p/PTEN/Akt pathway.Clinical and translational medicine · 2025Article
- Review
- Radiation dose escalation in locally advanced oesophageal cancer: a systematic review and hierarchical Bayesian meta-analysis.EClinicalMedicine · 2025Article
- The recent progress of tumor cell-derived exosomes in the pathogenesis, diagnosis and therapeutic strategies of tumors.Journal of translational medicine · 2025Review
- Unveiling the multifaceted roles of extracellular vesicles in cancer: insights from molecular imaging and engineering strategies.Acta biochimica et biophysica Sinica · 2025Review
- Revolutionizing cancer treatment: engineering mesenchymal stem cell-derived small extracellular vesicles.Cancer cell international · 2025Review
- Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Modulate Chemoradiotherapy Response in Cervical Cancer Spheroids.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Pathways and outputs orchestrated in tumor microenvironment cells by hypoxia-induced tumor-derived exosomes in pan-cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Current trends in theranostic applications of extracellular vesicles in cancer.Frontiers in oncology · 2025Review
- Exosomes in esophageal cancer: function and therapeutic prospects.Medical oncology (Northwood, London, England) · 2024Review
- The signature of extracellular vesicles in hypoxic breast cancer and their therapeutic engineering.Cell communication and signaling : CCS · 2024Review
- Novel Insights Into DLAT's Role in Alzheimer's Disease-Related Copper Toxicity Through Microglial Exosome Dynamics.CNS neuroscience & therapeutics · 2024Article
- The roles of exosomes in esophageal cancer.Discover oncology · 2024Review
- Current findings on the antitumor effects of metformin on esophageal squamous cell carcinoma (Review).Molecular and clinical oncology · 2024Review
- Extracellular vesicles in anti-tumor drug resistance: Mechanisms and therapeutic prospects.Journal of pharmaceutical analysis · 2024Review
- Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy.Biological procedures online · 2024Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundRadiotherapy resistance is a major obstacle in the treatment of oesophageal squamous cell carcinoma (OSCC). Hypoxia is a critical cause of radioresistance. However, the communication between hypoxic cells and aerobic cells via exosomes during the transfer of radiation resistance remains unclear.
methodsExo-miR-340-5p levels were analysed by RNA-seq and qRT-PCR. We co-cultured OSCC cells with isolated normoxic and hypoxic exosomes to study their impact on radiosensitivity. We used a specific exo-miR-340-5p mimic and knock-down retrovirus to explore the role of this miRNA in the transfer of radioresistance from hypoxic to normoxic cells. Dual-luciferase reporter and RIP assays were used to verify KLF10 as a putative target of miR-340-5p. Several in vitro assays were conducted and xenograft models were established to investigate the effect of exo-miR-340-5p on OSCC radiosensitivity. The plasma exo-miR-340-5p levels in OSCC patients were analysed to study the clinical value of this parameter.
resultsHypoxic exosomes alleviated radiation-induced apoptosis and accelerated DNA damage repair. miR-340-5p was highly expressed in hypoxic exosomes and was transferred into normoxic cells, where it induced radioresistance. Overexpression of miR-340-5p in normoxic OSCC cells mimicked the radioresistance of cells co-cultured with hypoxic exosomes. Knockdown of miR-340-5p in hypoxic exosomes reversed the radioresistance effect, indicating that exo-miR-340-5p is critical for hypoxic EV-transferred radioresistance. KLF10 was identified as the direct target of miR-340-5p. Moreover, metformin was found to increase the expression of KLF10 and enhance the radiosensitivity of OSCC. Higher levels of miR-340-5p in the plasma exosomes from OSCC patients are related to a poorer radiotherapy response and prognosis.
conclusionsHypoxic tumour cell-derived exosomal miR-340-5p confers radioresistance in OSCC by targeting KLF10/UVRAG, suggesting that miR-340-5p could be a potential biomarker and therapeutic target for the enhancement of radiosensitivity in OSCC. Metformin can increase KLF10 expression, which ameliorates the radioresistance induced by exo-miR-340-5p transfer. Therefore, metformin could be further investigated as a therapeutic option for the treatment of OSCC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.