Cancer-Secreted Exosomal MiR-620 Inhibits ESCC Aerobic Glycolysis via FOXM1/HER2 Pathway and Promotes Metastasis

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer death worldwide. MicroRNAs (MiRNAs) have been reported to regulate cell functions through exosomes. Through the Gene Expression Omnibus (GEO) database, miR-620 was selected as a serum miRNA highly expressed in ESCC, but its detailed role in ESCC has not been explored. Tumor-secreted miRNAs have been reported to promote cancer metastasis through reprogramming the aerobic glycolysis of lung fibroblasts. Therefore, we intended to verify whether exosomal miR-620 secreted in ESCC cells may regulate the aerobic glycolysis of lung fibroblasts. METHODS: The effect of miR-620 on the aerobic glycolysis of ESCC cells was firstly verified through bioinformatics prediction and mechanism assays. Exosomes secreted from ESCC cells was detected, and the influence of exosomal miR-620 in regulating the aerobic glycolysis of lung fibroblasts was then verified both in vitro and in vivo. RESULTS: MiR-620 inhibited ESCC malignancy and suppressed the aerobic glycolysis of ESCC cells via targeting Forkhead box M1 (FOXM1) and human epidermal growth factor receptor 2 (HER2). Moreover, exosomal miR-620 was highly secreted in ESCC and could regulate HFL1 aerobic glycolysis via FOXM1/HER2 signaling. Furthermore, exosomal miR-620 could promote ESCC metastasis by reprogramming the aerobic glycolysis of lung fibroblasts (HFL1). CONCLUSION: Exosomal miR-620 secreted by ESCC cells inhibited the aerobic glycolysis via FOXM1/HER2 axis and promoted cancer metastasis.