Clarification of the Role of miR-9 in the Angiogenesis, Migration, and Autophagy of Endothelial Progenitor Cells Through RNA Sequence Analysis.

Clarification of the Role of miR-9 in the Angiogenesis, Migration, and Autophagy of Endothelial Progenitor Cells Through RNA Sequence Analysis.
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通过 RNA 序列分析阐明 miR-9 在内皮祖细胞血管生成、迁移和自噬中的作用。

DOI:
10.1177/0963689720963936
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发表时间:
2020-01
影响因子:
3.3
通讯作者:
Li XQ
Li XQ
中科院分区:
医学4区
文献类型:
--
作者:
Zhu J;Sun LL;Li WD;Li XQ

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我们先前已经报道,miR-9通过AKT自噬途径靶向瞬时受体潜能Melastatin 7,促进内皮祖细胞(EPC)的归巢、增殖和血管生成。通过这种方式,miR-9促进深静脉血栓形成(DVT)后的血栓溶解和再通。然而,miR-9对内皮祖细胞信使RNA(MRNA)表达谱的影响尚不清楚。目前的研究包括对miR-9调节内皮祖细胞血管生成的潜在机制的全面探索,并强调了治疗DVT的潜在策略。RNA序列分析显示,在miR-9高表达的EPC和阴性对照组中,有4068个mRNAs表达存在差异,其中1894个表达上调,2174个表达下调。基因本体论和京都百科全书的基因和基因组途径分析表明,这些mRNAs主要参与调节细胞的增殖/迁移过程/途径和自噬途径,这两者都是潜在的基于EPC的DVT治疗策略。逆转录定量聚合酶链式反应证实了与EPC血管生成、迁移和自噬相关的mRNA表达的变化。我们还证明miR-9通过直接或间接调节FGF5促进EPC迁移和血管生成。总之,miR-9增强VEGFA、FGF5、FGF12、MMP2、MMP7、MMP10、MMP11、MMP24和ATG7的表达,从而影响EPC的迁移、血管生成和自噬。我们对miR-9调节的内皮祖细胞的mRNA表达进行了全面的评估,并强调了开发新的DVT治疗干预措施的潜在靶点。
We have previously reported that miR-9 promotes the homing, proliferation, and angiogenesis of endothelial progenitor cells (EPCs) by targeting transient receptor potential melastatin 7 via the AKT autophagy pathway. In this way, miR-9 promotes thrombolysis and recanalization following deep vein thrombosis (DVT). However, the influence of miR-9 on messenger RNA (mRNA) expression profiles of EPCs remains unclear. The current study comprises a comprehensive exploration of the mechanisms underlying the miR-9-regulated angiogenesis of EPCs and highlights potential treatment strategies for DVT. We performed RNA sequence analysis, which revealed that 4068 mRNAs were differentially expressed between EPCs overexpressing miR-9 and the negative control group, of which 1894 were upregulated and 2174 were downregulated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that these mRNAs were mainly involved in regulating cell proliferation/migration processes/pathways and the autophagy pathway, both of which represent potential EPC-based treatment strategies for DVT. Reverse transcriptase quantitative polymerase chain reaction confirmed the changes in mRNA expression related to EPC angiogenesis, migration, and autophagy. We also demonstrate that miR-9 promotes EPC migration and angiogenesis by regulating FGF5 directly or indirectly. In summary, miR-9 enhances the expression of VEGFA, FGF5, FGF12, MMP2, MMP7, MMP10, MMP11, MMP24, and ATG7, which influences EPC migration, angiogenesis, and autophagy. We provide a comprehensive evaluation of the miR-9-regulated mRNA expression in EPCs and highlight potential targets for the development of new therapeutic interventions for DVT.
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