Research Paper|Volume 13, Issue 3|pp 3588—3604

Downregulation of circFASTKD1 ameliorates myocardial infarction by promoting angiogenesis

Wen-Qing Gao^1,^2,³, Xiao-Min Hu^1,^2,³, Qiang Zhang^1,^2,³, Lan Yang⁴, Xin-Ze Lv⁵, Shuang Chen⁴, Peng Wu^1,^2,³, Da-Wei Duan^1,^2,³, Yu-Heng Lang^1,^2,³, Meng Ning^1,^2,³, Ke-Guan Lai⁵, Zhi-Yuan Zhang⁴, Bin Liang⁴, Jing-Yu Bao⁵, Hai-Dong Wu⁴, Tong Li^1,^2,³

¹The Third Central Hospital of Tianjin, Tianjin, China
²Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
³Artificial Cell Engineering Technology Research Center, Tianjin, China
⁴Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China
⁵Good Laboratory Practice Center, Tianjin International Joint Academy of Biomedicine, Tianjin, China

* Equal contribution

Received: May 28, 2020Accepted: September 29, 2020Published: December 19, 2020

https://doi.org/10.18632/aging.202305

Copyright: © 2020 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Circular RNAs (circRNAs), a novel class of endogenous long non-coding RNAs, have attracted considerable attention due to their closed continuous loop structure and potential clinical value. In this study, we investigated the function of circFASTKD1 in vascular endothelial cells. CircFASTKD1 bound directly to miR-106a and relieved its inhibition of Large Tumor Suppressor Kinases 1 and 2, thereby suppressing the Yes-Associated Protein signaling pathway. Under both normal and hypoxic conditions, the ectopic expression of circFASTKD1 reduced the viability, migration, mobility and tube formation of vascular endothelial cells, whereas the downregulation of circFASTKD1 induced angiogenesis by promoting these processes. Moreover, downregulation of circFASTKD1 in mice improved cardiac function and repair after myocardial infarction. These findings indicate that circFASTKD1 is a potent inhibitor of angiogenesis after myocardial infarction and that silencing circFASTKD1 exerts therapeutic effects during hypoxia by stimulating angiogenesis in vitro and in vivo.