长链非编码 RNA MAGI2-AS3 通过下调 miR-223-3p 促进骨折愈合。
LncRNA MAGI2-AS3 promotes fracture healing through downregulation of miR-223-3p.
机构信息
Department of Orthopedics, Xi'an International Medical Center Hospital, Xi'an, 710000, China.
Department of Orthopedics, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China.
出版信息
J Orthop Surg Res. 2024 Jun 22;19(1):370. doi: 10.1186/s13018-024-04850-5.
BACKGROUND
Long non-coding RNAs (LncRNAs) are recognized as a pivotal element in the processes of fracture healing and the osteogenic differentiation of stem cells. This study investigated the molecular mechanism and regulatory significance of lncRNA MAGI2-AS3 (MAGI2-AS3) in fracture healing.
METHODS
Serum levels of MAGI2-AS3 in patients with normal and delayed fracture healing were verified by RT-qPCR assays. The predictive efficacy of MAGI2-AS3 for delayed fracture healing was analyzed by ROC curve. Osteogenic markers were quantified by RT-qPCR assays. MC3T3-E1 cell viability was detected using CCK-8 assay, and flow cytometry was utilized to measure cell apoptosis. The dual-luciferase reporter gene assay was used to determine the targeted binding between MAGI2-AS3 and miR-223-3p.
RESULTS
Serum MAGI2-AS3 expression was decreased in patients with delayed fracture healing compared with patients with normal healing. Elevated MAGI2-AS3 resulted in an upregulation of the proliferative capacity of MC3T3-E1 cells and a decrease in mortality, along with increased levels of both osteogenic markers. However, after transfection silencing MAGI2-AS3, the trend was reversed. Additionally, miR-223-3p was the downstream target of MAGI2-AS3 and was controlled by MAGI2-AS3. miR-223-3p mimic reversed the promoting effects of MAGI2-AS3 overexpression on osteogenic marker levels and cell growth, and induced cell apoptosis.
CONCLUSION
The upregulation of MAGI2-AS3 may expedite the healing of fracture patients by targeting miR-223-3p, offering a novel biomarker for diagnosing patients with delayed healing.
背景
长链非编码 RNA（lncRNA）被认为是骨折愈合和干细胞成骨分化过程中的关键因素。本研究探讨了 lncRNA MAGI2-AS3（MAGI2-AS3）在骨折愈合中的分子机制和调控意义。
方法
通过 RT-qPCR 检测正常和延迟骨折愈合患者血清中 MAGI2-AS3 的水平。通过 ROC 曲线分析 MAGI2-AS3 对延迟骨折愈合的预测效能。通过 RT-qPCR 检测成骨标志物的表达。通过 CCK-8 法检测 MC3T3-E1 细胞活力，通过流式细胞术检测细胞凋亡。通过双荧光素酶报告基因实验确定 MAGI2-AS3 与 miR-223-3p 的靶向结合。
结果
与正常愈合患者相比，延迟骨折愈合患者血清中 MAGI2-AS3 的表达降低。MAGI2-AS3 水平升高可上调 MC3T3-E1 细胞的增殖能力，降低细胞死亡率，同时增加成骨标志物的水平。然而，转染沉默 MAGI2-AS3 后，趋势发生逆转。此外，miR-223-3p 是 MAGI2-AS3 的下游靶基因，受 MAGI2-AS3 调控。miR-223-3p 模拟物逆转了 MAGI2-AS3 过表达对成骨标志物水平和细胞生长的促进作用，并诱导细胞凋亡。
结论
MAGI2-AS3 的上调可能通过靶向 miR-223-3p 加速骨折患者的愈合，为诊断延迟愈合患者提供了一种新的生物标志物。
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