The miR-148/152 family contributes to angiogenesis of human pluripotent stem cell- derived endothelial cells by inhibiting MEOX2

Fengyue Ding; Hongchun Wu; Xinglong Han; Xue Jiang; Yang Xiao; Yuanyuan Tu; Miao Yu; Wei Lei; Shijun Hu

doi:10.1016/j.omtn.2023.04.020

The miR-148/152 family contributes to angiogenesis of human pluripotent stem cell- derived endothelial cells by inhibiting MEOX2

Mol Ther Nucleic Acids. 2023 Apr 23:32:582-593. doi: 10.1016/j.omtn.2023.04.020. eCollection 2023 Jun 13.

Authors

Fengyue Ding¹, Hongchun Wu¹, Xinglong Han¹, Xue Jiang¹, Yang Xiao¹, Yuanyuan Tu¹, Miao Yu¹, Wei Lei¹, Shijun Hu¹

Affiliation

¹ Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou 215000, China.

Abstract

Human pluripotent stem cell-derived endothelial cells (hPSC-ECs) represent a promising source of human ECs urgently needed for the study of cardiovascular disease mechanisms, cell therapy, and drug screening. This study aims to explore the function and regulatory mechanism of the miR-148/152 family consisting of miR-148a, miR-148b, and miR-152 in hPSC-ECs, so as to provide new targets for improving EC function during the above applications. In comparison with the wild-type (WT) group, miR-148/152 family knockout (TKO) significantly reduced the endothelial differentiation efficiency of human embryonic stem cells (hESCs), and impaired the proliferation, migration, and capillary-like tube formatting abilities of their derived ECs (hESC-ECs). Overexpression of miR-152 partially restored the angiogenic capacity of TKO hESC-ECs. Furthermore, the mesenchyme homeobox 2 (MEOX2) was validated as the direct target of miR-148/152 family. MEOX2 knockdown resulted in partial restoration of the angiogenesis ability of TKO hESC-ECs. The Matrigel plug assay further revealed that the in vivo angiogenic capacity of hESC-ECs was impaired by miR-148/152 family knockout, and increased by miR-152 overexpression. Thus, the miR-148/152 family is crucial for maintaining the angiogenesis ability of hPSC-ECs, and might be used as a target to enhance the functional benefit of EC therapy and promote endogenous revascularization.

Keywords: MT: Non-coding RNAs; angiogenesis; endothelial cells; human pluripotent stem cells; mesenchyme homeobox 2; miR-148/152 family.