Cancer-derived fucosylated exosomal miR-6842-3p as a novel marker promotes ESCC angiogenesis and metastasis via the PTEN/AKT/mTOR/IRF1/CXCL10 axis

Tumour-derived fucosylated exosomes (FUC-Exo) play significant roles in cancer progression. However, the functions and mechanisms of fucosylated exosome-derived miRNAs in oesophageal squamous cell carcinoma (ESCC) remain largely unknown. Using lentil lectin (LCA)-coated magnetic beads for FUC-Exo isolation, small RNA sequencing and RT-qPCR identified miR-6842-3p as a novel ESCC biomarker. In vitro and in vivo assays explored its oncogenic role and pro-angiogenic function. Dual-luciferase assays, ChIP-qPCR, western blot and rescue assays were performed to elucidate angiogenic mechanisms. miR-6842-3p is upregulated in ESCC tissues and serum FUC-Exo, significantly associated with advanced clinical stages, worse prognosis and serves as an early diagnostic biomarker for ESCC. miR-6842-3p acts as an oncogene, promoting tumour growth, metastasis and angiogenesis in ESCC. Tumour-derived fucosylated exosomal miR-6842-3p, when internalised by HUVECs, downregulates PTEN, triggering the phosphorylation of AKT and mTOR. This is followed by the inhibition of IRF1 expression, thereby downregulating CXCL10 expression and driving angiogenesis. These findings elucidate that miR-6842-3p functions as a key driver of ESCC growth, metastasis and angiogenesis. Fucosylated exosomal miR-6842-3p promotes angiogenesis by mediating the PTEN/AKT/mTOR/IRF1/CXCL10 axis, highlighting its potential as a novel biomarker and therapeutic target for ESCC.