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. 2019 Dec;462(1-2):75-83.
doi: 10.1007/s11010-019-03611-x. Epub 2019 Aug 21.

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

Ximeng Ji #  1   2 , Hao Hua #  3 , Yinying Shen  1 , Shoushan Bu  4 , Sheng Yi  5
Affiliations

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

Ximeng Ji et al. Mol Cell Biochem. 2019 Dec.

Abstract

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.

Keywords: Endothelial cells; Let-7d; Migration; Proliferation; Tubulogenesis.

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