A mammalian mirtron miR-1224 promotes tube-formation of human primary endothelial cells by targeting anti-angiogenic factor epsin2

作者：Sakai Eiko; Miura Yusuke; Suzuki Kouyama Emi; Oka Kengo; Tachibana Masashi; Kawabata Kenji; Sakurai Fuminori; Mizuguchi Hiroyuki^*

来源：Scientific Reports, 2017, 7(1): 5541.

DOI：10.1038/s41598-017-05782-3

Angiogenesis, new vessel formation from pre-existing vessels, is a highly conserved event through vertebrates. However, the system for tuning angiogenesis by species-intrinsic factors is totally unknown. miR-1224 is a member of mammal-specific mirtrons, which were identified as non-canonical microRNAs. We found that the expression of miR-1224 was upregulated in capillary-like tube-forming human umbilical vein endothelial cells on Matrigel. Enforced expression of miR-1224 stimulated tube formation, whereas repression of endogenous miR-1224 inhibited formation. Enforced expression of miR-1224 enhanced VEGF signaling and repressed NOTCH signaling. The adaptor protein of clathrindependent endocytosis, epsin2, which has been shown to be a suppressor of angiogenesis, was a direct target of miR-1224. Knockdown of EPN2 stimulated tube formation, while overexpression of EPN2 repressed miR-1224-mediated stimulation. Our findings indicate that miR-1224 is a mammal specific modulator of angiogenesis.

• 出版日期2017-7-17