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

Abstract

AbstractBackgroundOral 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.MethodsEffects 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.ResultsHypoxic 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.ConclusionsWe showed that hypoxia led to OSCC‐derived exosome mediated transfer of miR‐1825 to HUVECs and enhanced angiogenesis in OSCC in vitro.