Hypoxia‐induced tumor exosomes promote angiogenesis through <scp>miR</scp>‐1825/<scp>TSC2</scp>/<scp>mTOR</scp> axis in oral squamous cell carcinoma

Abstract

BACKGROUND: Oral squamous cell carcinoma (OSCC) is characterized by enhanced angiogenesis resulting in poor prognosis despite improvements in diagnostic/therapeutic techniques. Here, we aimed at investigating potential roles of miR-1825 enclosed in OSCC-derived exosomes on angiogenesis under hypoxic conditions. METHODS: Effects of miR-1825 mimic/inhibitor as well as hypoxia-induced tumor derived exosomes on human umbilical vein endothelial cells (HUVECs) were evaluated using cell viability, migration/invasion, tube formation, and spheroid-based 3D angiogenesis assays. RESULTS: Hypoxic conditions caused significant increase in miR-1825 levels in OSCC cells and hiTDEs. miR-1825 alone and within hiTDEs promoted endothelial cell viability, migration, invasion, and angiogenic potential, which is reversed via inhibition of miR-1825 expression. miR-1825 within hiTDEs altered the angiogenesis potential of HUVEC cells via deregulation of TSC2/mTOR axis. CONCLUSIONS: We showed that hypoxia led to OSCC-derived exosome mediated transfer of miR-1825 to HUVECs and enhanced angiogenesis in OSCC in vitro.