Details

Autor(en) / Beteiligte

• Gu, Yuan
• Pais, Gianni
• Becker, Vivien
• Körbel, Christina
• Ampofo, Emmanuel
• Ebert, Elke
• Hohneck, Johannes
• Ludwig, Nicole
• Meese, Eckart
• Bohle, Rainer M.
• Zhao, Yingjun
• Menger, Michael D.
• Laschke, Matthias W.

Titel

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

Ist Teil von

• Molecular therapy. Nucleic acids, 2021-12, Vol.26, p.849-864

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2021

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 is preferentially and highly expressed in ECs, while its endothelial level is significantly downregulated in human non-small cell lung cancer (NSCLC) tissues when compared to matched nontumor lung tissues. This reduction of endothelial miR-22 is possibly induced by NSCLC cell-secreted interleukin-1β and subsequently activated transcription factor nuclear factor-κB. Endothelial miR-22 functions as a potent angiogenesis inhibitor that inhibits all of the key angiogenic activities of ECs and consequently NSCLC growth through directly targeting sirtuin 1 and fibroblast growth factor receptor 1 in ECs, leading to inactivation of AKT/mammalian target of rapamycin signaling. These findings provide insight into the molecular mechanisms of NSCLC angiogenesis and indicate that endothelial miR-22 represents a potential target for the future antiangiogenic treatment of NSCLC. [Display omitted] The present study demonstrates that miR-22 is highly expressed in endothelial cells and inhibits their angiogenic activity via targeting sirtuin 1 and fibroblast growth factor receptor 1. Hence, endothelial miR-22 represents a potential biomarker and therapeutic target for the future antiangiogenic treatment of non-small cell lung cancer.