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ORIGINAL RESEARCH article

Front. Genet.
Sec. Stem Cell Research
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1407671

Identification of Key miRNAs and Target Genes in Extracellular Vesicles Derived from Low-Intensity Pulsed Ultrasound-Treated Stem Cells

Provisionally accepted
Xin Yin Xin Yin 1,2,3Jialian Yi Jialian Yi 3*Fugang Mao Fugang Mao 3*Qixing Tang Qixing Tang 3*Xinyu Zhang Xinyu Zhang 3*Xiaoyu Yang Xiaoyu Yang 3*Hongqing Xie Hongqing Xie 3*Lin-Ping Wang Lin-Ping Wang 3Shuifen Sun Shuifen Sun 3*Yu Xin Yu Xin 3*Jie Liu Jie Liu 3Lihong Jiang Lihong Jiang 1,2,3*
  • 1 Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China
  • 2 The Affiliated Hospital of Kunming University of Science and Technology, kunming, China
  • 3 The First People’s Hospital of Yunnan Province, Kunming, Yunnan Province, China

The final, formatted version of the article will be published soon.

    Objectives—This study aimed to investigate the impact of low-intensity pulsed ultrasound (LIPUS) treatment on the miRNA and mRNA profiles of stem cell-derived extracellular vesicles (EVs). Specifically, it sought to identify key miRNAs and their target mRNAs associated with enhanced therapeutic efficacy in LIPUS-treated stem cell-derived EVs. Methods—Utilizing miRNA deep-sequencing data from the Gene Expression Omnibus database, differential gene analysis was performed. MiRNA-mRNA target analysis, functional and pathway enrichment analysis, protein-protein interaction network construction, and hub gene identification were conducted. Validation of differentially expressed miRNAs was performed via RT-qPCR in human umbilical cord mesenchymal stem cells (hUC-MSCs) treated with LIPUS. Results—Ten differentially expressed miRNAs were identified, with six upregulated and four downregulated miRNAs in LIPUS-treated stem cell-derived EVs. Functional enrichment analysis revealed involvement in biological processes such as regulation of metabolic processes, cellular component organization, and response to stress, as well as signaling pathways like cell cycle, MAPK signaling, and Hippo signaling. Protein-protein interaction network analysis identified key hub genes including MYC, GAPDH, HSP90AA1, EP300, JUN, PTEN, DAC1, STAT3, HSPA8, and HIF1A associated with LIPUS treatment. RT-qPCR validation confirmed differential expression of selected miRNAs (hsa-miR-933, hsa-miR-3943, hsa-miR-4633-5p, hsa-miR-592, hsa-miR-659-5p, hsa-miR-4766-3p) in LIPUS-treated hUC-MSCs. Conclusion—This study sheds light on the potential therapeutic mechanisms underlying LIPUS-treated stem cell-derived EVs. The identified differentially expressed miRNAs and their potential target mRNAs offer valuable insights into the biological processes influenced by LIPUS treatment. While further investigation is necessary to validate their roles as therapeutic targets, this study lays the groundwork for future research on optimizing SC-EV therapy with LIPUS preconditioning.

    Keywords: Stem Cells, Extracellular vesicles (EVs), Low-intensity pulsed ultrasound (LIPUS), MicroRNAs, bioinformatics, membrane vesicles

    Received: 27 Mar 2024; Accepted: 18 Dec 2024.

    Copyright: © 2024 Yin, Yi, Mao, Tang, Zhang, Yang, Xie, Wang, Sun, Xin, Liu and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jialian Yi, The First People’s Hospital of Yunnan Province, Kunming, Yunnan Province, China
    Fugang Mao, The First People’s Hospital of Yunnan Province, Kunming, Yunnan Province, China
    Qixing Tang, The First People’s Hospital of Yunnan Province, Kunming, Yunnan Province, China
    Xinyu Zhang, The First People’s Hospital of Yunnan Province, Kunming, Yunnan Province, China
    Xiaoyu Yang, The First People’s Hospital of Yunnan Province, Kunming, Yunnan Province, China
    Hongqing Xie, The First People’s Hospital of Yunnan Province, Kunming, Yunnan Province, China
    Shuifen Sun, The First People’s Hospital of Yunnan Province, Kunming, Yunnan Province, China
    Yu Xin, The First People’s Hospital of Yunnan Province, Kunming, Yunnan Province, China
    Lihong Jiang, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China

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