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

MicroRNAs (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)1and fibroblast growth factor receptor (FGFR)1in 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.