Down-Regulation of lncRNA XIST Ameliorates Lipoprotein(a) Induced Endothelial Progenitor Cell Damage via Modulating miR-126/PLK2 Axis

crossref(2021)

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摘要
Abstract Background Recent studies have discovered that lncRNAs regulate lipoprotein (LP) (a)-mediated endothelial progenitor cells (EPCs) damage through sponging miRNAs. However, the role of XIST in EPC remains unknown. Method: Firstly, LP(a)(100 ng/mL) was used to treat EPCs for 6 hours. Then, the apoptosis, proliferation, migration, adhesion, angiogenesis of EPCs were detected. Moreover, overexpression of XIST or miR-126 on EPCs were built. Mechanistically, bioinformatics database, dual-luciferase reporter assay and RIP were used to found the binding relationships between XIST and miR-126, miR-126 and PLK2. Results Presently, we found LP(a) treatment significantly induced apoptosis, attenuated the proliferation, migration, adhesion, angiogenesis of EPCs. While knocking down XIST or overexpression miR-126 significantly reversed LP(a) induced damage on EPCs. Moreover, forced overexpression of XIST partially offset the protective effects of overexpressing miR-126 on EPC. Mechanistically, through bioinformatics database (http://starbase.sysu.edu.cn/index.php), we found potential binding relationships between XIST and miR-126, miR-126 and PLK2. Furthermore, the dual-luciferase reporter assay and RIP experiment confirmed the targeted binding between them. Conclusion Collectively, the above results confirmed that down-regulating XIST improved LP(a)-induced EPC damage by regulating the miR-126/PLK2 axis, and the XIST/miR-126/PLK2 axis exerted an essential role in regulating EPC function.
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