Suppression of endothelial miR-22-3p mediates non-small cell lung cancer cell-induced angiogenesis

AbstractMicroRNAs (miRNAs) expressed in endothelial cells (ECs) are powerful regulators of angiogenesis, which is essential for tumor growth and metastasis. Here, we demonstrated that miR-22-3p (miR-22) is preferentially and highly expressed in ECs, while its endothelial level is significantly down-regulated in human non-small cell lung cancer (NSCLC) tissues when compared to matched non-tumor lung tissues. This reduction of endothelial miR-22 is induced by NSCLC cell-secreted tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Endothelial miR-22 functions as a potent angiogenesis inhibitor that inhibits all the key angiogenic activities of ECs and consequently NSCLC growth through directly targeting sirtuin (SIRT) 1 and fibroblast growth factor receptor (FGFR) 1 in ECs, leading to inactivation of AKT/mammalian target of rapamycin (mTOR) signaling. These novel findings provide insight into the molecular mechanisms of NSCLC angiogenesis and indicate that endothelial miR-22 represents a potential target for the future anti-angiogenic treatment of NSCLC.