Let-7d modulates the proliferation, migration, tubulogenesis of endothelial cells.

Endothelial cells are important components of peripheral nerve stumps that contribute to Schwann cell migration and peripheral nerve regeneration. Let-7d modulates the phenotype of Schwann cells and affected peripheral nerve regeneration. However, the regulatory roles of let-7d on endothelial cells remain undetermined. In this study, by transfecting cultured human umbilical vein endothelial cells (HUVECs) with let-7d mimic or let-7d inhibitor, we investigated the biological effects of let-7d on endothelial cells. EdU proliferation assay showed that upregulated let-7d decreased the proliferation rates of HUVECs while downregulated let-7d increased the proliferation rates of HUVECs. Transwell-based migration assay and wound-healing assay demonstrated that let-7d inhibited the migration ability of HUVECs. Matrigel assay suggested that let-7d decreased the numbers of formed meshes and suppressed the tubulogenesis of HUVECs. RNA sequencing, bioinformatic analysis, gene expression validation, and luciferase assay suggested that let-7d directly targeted interferon-induced protein 44 like (IFI44L) gene and negatively regulated the expression of IFI44L. Taken together, our study illuminated the inhibitory roles of let-7d on the proliferation, migration, and tubulogenesis of endothelial cells, identified the target gene of let-7d, and deepened the understanding of the biological effects of let-7d on key elements of peripheral nerve regeneration.