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

• Main Authors: Yuan Gu (Author), Gianni Pais (Author), Vivien Becker (Author), Christina Körbel (Author), Emmanuel Ampofo (Author), Elke Ebert (Author), Johannes Hohneck (Author), Nicole Ludwig (Author), Eckart Meese (Author), Rainer M. Bohle (Author), Yingjun Zhao (Author), Michael D. Menger (Author), Matthias W. Laschke (Author)
• Format: Book
• Published: Elsevier, 2021-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2162-2531; 10.1016/j.omtn.2021.10.003
• Keywords: AKT; angiogenesis; endothelial cells; FGFR1; IL-1β; miR-22; Therapeutics. Pharmacology; RM1-950
• Source: Molecular Therapy: Nucleic Acids, Vol 26, Iss , Pp 849-864 (2021)

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.