Hypoxic tumour cell-derived exosomal miR-340-5p promotes radioresistance of oesophageal squamous cell carcinoma via KLF10

Abstract Background Radiotherapy resistance is a major obstacle in the treatment of oesophageal squamous cell carcinoma (OSCC). Hypoxia critical cause radioresistance. However, communication between hypoxic cells and aerobic via exosomes during transfer radiation remains unclear. Methods Exo-miR-340-5p levels were analysed by RNA-seq qRT-PCR. We co-cultured OSCC with isolated normoxic to study their impact on radiosensitivity. used specific exo-miR-340-5p mimic knock-down retrovirus explore role this miRNA radioresistance from cells. Dual-luciferase reporter RIP assays verify KLF10 as putative target miR-340-5p. Several vitro conducted xenograft models established investigate effect The plasma patients clinical value parameter. Results Hypoxic alleviated radiation-induced apoptosis accelerated DNA damage repair. miR-340-5p was highly expressed transferred into cells, where it induced Overexpression mimicked exosomes. Knockdown reversed effect, indicating that for EV-transferred identified direct Moreover, metformin found increase expression enhance radiosensitivity OSCC. Higher are related poorer radiotherapy response prognosis. Conclusions tumour cell-derived exosomal confers targeting KLF10/UVRAG, suggesting could be potential biomarker therapeutic enhancement Metformin can expression, which ameliorates transfer. Therefore, further investigated option