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Hypoxia is a common characteristic of solid tumors and is associated with cancer progression and poor outcomes. However, the roles and specific mechanisms of exosomes and hypoxia during cancer progression still remain unclear. Herein, we found that exosomes secreted from hypoxic colorectal cancer (CRC) cells promoted the proliferation, migration, invasion, and metastasis of normoxic CRC cells, and these hypoxic exosomes exerted their biological effects depending on miR-410-3p. We discovered that miR-410-3p was highly enriched in hypoxic CRC-derived exosomes in a HIF1α or HIF2α-dependent manner, and miR-410-3p levels positively associated with poor prognosis of CRC. Moreover, decreased PTEN levels caused by hypoxic CRC cells-derived exosomal miR-410-3p increased activation of PI3K/Akt as well as tumor progression. Conversely, inhibition of miR-410-3p or PI3K/Akt signaling pathway effectively decreased hypoxic CRC cells-derived exosomes-mediated tumor progression. In conclusion, our findings indicate that the hypoxic microenvironment in CRC may promote tumor cells to release miR-410-3p-rich exosomes that are transferred to normoxic cells to enhance tumor progression, revealing a new investigation into the therapeutic targets of exosome for CRC treatment.

Exosomes Derived from Hypoxic Colorectal Cancer Cells Transfer miR-410-3p to Regulate Tumor Progression