长链非编码 RNA MEG3 通过靶向 miR-532-5p 促进 MEFs 中的 PDK4/GSK-3/-Catenin 轴。

lncRNA MEG3 Promotes PDK4/GSK-3/-Catenin Axis in MEFs by Targeting miR-532-5p.

机构信息

Department of Blood Transfusion, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.

出版信息

Oxid Med Cell Longev. 2023 Feb 1;2023:3563663. doi: 10.1155/2023/3563663. eCollection 2023.

DOI:10.1155/2023/3563663

PMID:36778210

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9908332/

Abstract

Studies reported the positive and negative osteogenic effects of MEG3 in mesenchymal stem cells (MSCs). This study aims at clarifying the osteogenic potential of MEG3 and the underlying mechanism. Bone morphogenetic protein 9- (BMP9-) transfected MSCs were recruited as an osteogenic model , and ectopic bone formation were used to explore the effect of MEG3 on osteogenesis. We found that overexpression of MEG3 facilitated BMP9-induced osteogenic markers, ALP activities, and matrix mineralization. However, knockdown of MEG3 attenuated BMP9-induced osteogenic markers. MEG3 increased the phosphorylation of GSK-3 and the protein level of -catenin. Pyruvate dehydrogenase kinase 4 (PDK4) can also combine with GSK-3 and increase the latter phosphorylation. Moreover, MEG3 increased the mRNA level of PDK4. The ceRNA analysis showed that MEG3 may regulate the expression of PDK4 via microRNA 532-5p (miR-532-5p). The MEG3-enhanced GSK-3/-catenin axis can be attenuated by miR-532-5p, and miR-532-5p inhibitor partly rescued endogenous PDK4 and MEG3-mediated expression of PDK4. MEG3 may potentiate PDK4 and GSK-3/-catenin by inhibiting miR-532-5p.

摘要

研究报道了 MEG3 在间充质干细胞（MSCs）中具有正向和负向成骨作用。本研究旨在阐明 MEG3 的成骨潜能及其潜在机制。招募骨形态发生蛋白 9（BMP9）转染的 MSCs 作为成骨模型，利用异位骨形成来探索 MEG3 对成骨的影响。我们发现，MEG3 的过表达促进了 BMP9 诱导的成骨标志物、ALP 活性和基质矿化。然而，MEG3 的敲低减弱了 BMP9 诱导的成骨标志物。MEG3 增加了 GSK-3 的磷酸化和 -catenin 的蛋白水平。丙酮酸脱氢酶激酶 4（PDK4）也可以与 GSK-3 结合并增加后者的磷酸化。此外，MEG3 增加了 PDK4 的 mRNA 水平。ceRNA 分析表明，MEG3 可能通过 microRNA 532-5p（miR-532-5p）来调节 PDK4 的表达。MEG3 增强的 GSK-3/-catenin 轴可以被 miR-532-5p 减弱，而 miR-532-5p 抑制剂部分挽救了内源性 PDK4 和 MEG3 介导的 PDK4 表达。MEG3 可能通过抑制 miR-532-5p 来增强 PDK4 和 GSK-3/-catenin。