LncRNA WTAPP1 Promotes Migration and Angiogenesis of Endothelial Progenitor Cells via MMP1 Through MicroRNA 3120 and Akt/PI3K/Autophagy Pathways
LncRNA WTAPP1 Promotes Migration and Angiogenesis of Endothelial Progenitor Cells via MMP1 Through MicroRNA 3120 and Akt/PI3K/Autophagy Pathways
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LncRNA WTAPP1 通过 MicroRNA 3120 和 Akt/PI3K/自噬途径通过 MMP1 促进内皮祖细胞的迁移和血管生成
DOI：
10.1002/stem.2904
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发表时间：
2018-12-01
期刊：
影响因子：
5.2
通讯作者：
Li, Xiao-Qiang
中科院分区：
文献类型：
--
作者：
Li, Wen-Dong;Zhou, Dong-Ming;Li, Xiao-Qiang
在血栓事件中，内皮祖细胞（EPCs）的有效募集和血管生成至关重要。然而，EPC募集和血管生成调控的细节尚未完全确定。本研究的目的是确定长链非编码（lnc）RNA Wilms肿瘤1相关蛋白假基因1 （WTAPP1）在调控EPCs迁移和血管生成中的作用。从人外周血中分离EPCs，用流式细胞术对其进行鉴定，然后进行慢病毒介导的lncRNA WTAPP1过表达和敲低。采用Scratch法、Transwell法、体外和体内管形成法分别测定细胞迁移、侵袭和血管生成能力。此外，对与lncRNA WTAPP1相互作用的mirna进行了微阵列筛选、生物信息学预测、定量PCR和Western blot检测。Western blot检测WTAPP1、miR‐3120‐5P和MMP‐1在自噬通路中的关系。WTAPP1通过增加MMP‐1表达和激活PI3K/Akt/mTOR信号，积极调节EPCs的迁移、侵袭和体外和体内管形成。此外，WTAPP1含有一个推测的miR - 3120 - 5P结合位点。miR‐3120‐5P抑制WTAPP1降低了MMP‐1的水平。此外，我们证明了自噬途径的抑制参与了WTAPP1对EPC迁移和血管生成的影响。lncRNA WTAPP1是miR‐3120‐5p的诱骗分子，通过PI3K/Akt和自噬途径调节MMP‐1的表达，从而介导内皮细胞的细胞迁移和血管生成。作为潜在的治疗靶点，lncRNA WTAPP1可能在DVT的发病机制中发挥重要作用。干细胞2018；36:1863-12
Efficient recruitment and angiogenesis of endothelial progenitor cells (EPCs) are critical during a thrombus event. However, the details of EPC recruitment and the regulation of angiogenesis have not been fully determined. The aim of this study was to determine the role of the long noncoding (lnc)RNA Wilms tumor 1 associated protein pseudogene 1 (WTAPP1) in regulation of the migration and angiogenesis of EPCs. EPCs were isolated from human peripheral blood and characterized by flow cytometry, after which lentivirus‐mediated lncRNA WTAPP1 overexpression and knockdown were performed. Scratch assay, Transwell assay, and in vitro and in vivo tube formation assays were performed to measure cell migration, invasion, and angiogenic abilities, respectively. Moreover, a microarray screen, bioinformatic prediction, and quantitative PCR and Western blot of miRNAs interacting with lncRNA WTAPP1 were conducted. Western blot was carried out to elucidate the relationship among WTAPP1, miR‐3120‐5P, and MMP‐1 in the autophagy pathway. WTAPP1 positively regulated migration, invasion, and in vitro and in vivo tube formation in EPCs by increasing MMP‐1 expression and activating PI3K/Akt/mTOR signaling. Furthermore, WTAPP1 contains a putative miR‐3120‐5P binding site. Suppression of WTAPP1 by miR‐3120‐5P decreased the level of MMP‐1. In addition, we demonstrated that suppression of the autophagy pathway is involved in the effects of WTAPP1 on EPC migration and angiogenesis. The lncRNA WTAPP1, a molecular decoy for miR‐3120‐5p, regulates MMP‐1 expression via the PI3K/Akt and autophagy pathways, thereby mediating cell migration and angiogenesis in EPCs. Acting as a potential therapeutic target, the lncRNA WTAPP1 may play an important role in the pathogenesis of DVT. Stem Cells 2018;36:1863–12