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bioRxiv · 10.1101/2021.04.04.438401

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

Gu, Y.·Pais, G.·Becker, V.·Körbel, C.·Ampofo, E.·Ebert, E.·Hohneck, J.·Ludwig, N.·Meese, E.·Bohle, R. M.·Zhao, Y.·Menger, M. D.·Laschke, M. W.
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Abstract

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)- and interleukin (IL)-1{beta}. 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.

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Gu, Y., Pais, G., Becker, V., Körbel, C., Ampofo, E., Ebert, E., Hohneck, J., Ludwig, N., Meese, E., Bohle, R. M., Zhao, Y., Menger, M. D., Laschke, M. W.. 2021-04-06. Suppression of endothelial miR-22-3p mediates non-small cell lung cancer cell-induced angiogenesis. https://doi.org/10.1101/2021.04.04.438401

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