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鉴定和分析 DMD/mdx 原代肌母细胞中差异表达的 lncRNAs 及其 ceRNA 网络。

Identification and analysis of differentially expressed lncRNAs and their ceRNA networks in DMD/mdx primary myoblasts.

机构信息

Department of Physiological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, 02-776, Poland.

Department Animal Science, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran.

出版信息

Sci Rep. 2024 Oct 10;14(1):23691. doi: 10.1038/s41598-024-75221-7.

Abstract

This study explored the significance of long non-coding RNAs (lncRNAs), particularly their role in maintaining dystrophin protein stability and regulating myocyte proliferation and differentiation. The investigation focused on DMD/mdx mouse skeletal muscle primary myoblasts, aiming to identify lncRNAs potential as biomarkers and therapeutic targets for Duchenne muscular dystrophy (DMD). Utilizing CLC Genomics Workbench software, 554 differentially expressed lncRNAs were identified in DMD/mdx mice compared to wild-type (WT) control. Among them, 373 were upregulated, and 181 were downregulated. The study highlighted specific lncRNAs (e.g., 5930430L01Rik, Gm10143, LncRNA1490, LncRNA580) and their potential regulatory roles in DMD key genes like IGF1, FN1, TNNI1, and MYOD1. By predicting miRNA and their connections with lncRNA and mRNA (ceRNA network) using tools such as miRNet, miRSYSTEM and miRCARTA, the study revealed potential indirect regulation of Dystrophin, IGF1R and UTRN genes by identified lncRNAs (e.g. 2310001H17Rik-203, C130073E24Rik-202, LncRNA2767, 5930430L01Rik and LncRNA580). These findings suggest that the identified lncRNAs may play crucial roles in the development and progression of DMD through their regulatory influence on key gene expression, providing valuable insights for potential therapeutic interventions.

摘要

本研究探讨了长非编码 RNA(lncRNA)的意义,特别是它们在维持肌营养不良蛋白稳定性以及调节肌细胞增殖和分化方面的作用。该研究聚焦于 DMD/mdx 小鼠骨骼肌原代肌母细胞,旨在确定作为杜氏肌营养不良症(DMD)潜在生物标志物和治疗靶点的 lncRNA。利用 CLC Genomics Workbench 软件,在 DMD/mdx 小鼠与野生型(WT)对照之间鉴定出 554 个差异表达的 lncRNA。其中,373 个上调,181 个下调。该研究强调了特定的 lncRNA(例如,5930430L01Rik、Gm10143、LncRNA1490、LncRNA580)及其在 DMD 关键基因(如 IGF1、FN1、TNNI1 和 MYOD1)中的潜在调节作用。通过使用 miRNet、miRSYSTEM 和 miRCARTA 等工具预测 miRNA 及其与 lncRNA 和 mRNA 的连接(ceRNA 网络),研究揭示了所鉴定的 lncRNA 对 Dystrophin、IGF1R 和 UTRN 基因的潜在间接调节作用(例如,2310001H17Rik-203、C130073E24Rik-202、LncRNA2767、5930430L01Rik 和 LncRNA580)。这些发现表明,所鉴定的 lncRNA 可能通过对关键基因表达的调节作用,在 DMD 的发生和发展中发挥关键作用,为潜在的治疗干预提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/015c/11467414/c17b484b0bb7/41598_2024_75221_Fig1_HTML.jpg

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