Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (9): 1865-1870.doi: 10.4103/1673-5374.306092

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Transcriptomic analysis reveals essential microRNAs after peripheral nerve injury

Yu Wang, Shu Wang, Jiang-Hong He*   

  1. Key Laboratory for Neuroregeneration of Jiangsu Province and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
  • Online:2021-09-15 Published:2021-02-05
  • Contact: Jiang-Hong He, PhD, hejh@ntu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 31971276 (to JHH) and the Natural Science Foundation of Jiangsu Higher Education Institutions of China (Major Program), No. 19KJA320005 (to JHH). 

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Abstract: Studies have shown that microRNAs (miRNAs) mediate posttranscriptional regulation of target genes and participate in various physiological and pathological processes, including peripheral nerve injury. However, it is hard to select key miRNAs with essential biological functions among a large number of differentially expressed miRNAs. Previously, we collected injured sciatic nerve stumps at multiple time points after nerve crush injury, examined gene changes at different stages (acute, sub-acute, and post-acute), and obtained mRNA expression profiles. Here, we jointly analyzed mRNAs and miRNAs, and investigated upstream miRNAs of differentially expressed mRNAs using Ingenuity Pathway Analysis bioinformatic software. A total of 31, 42, 30, and 23 upstream miRNAs were identified at 1, 4, 7, and 14 days after rat sciatic nerve injury, respectively. Temporal expression patterns and biological involvement of commonly involved upstream miRNAs (miR-21, let-7, miR-223, miR-10b, miR-132, miR-15b, miR-127, miR-29a, miR-29b, and miR-9) were then determined at multiple time points. Expression levels of miR-21, miR-132, miR-29a, and miR-29b were robustly increased after sciatic nerve injury. Biological processes involving these miRNAs include multicellular organismal response to stress, positive regulation of the epidermal growth factor receptor signaling pathway, negative regulation of epithelial cell differentiation, and regulation of myocardial tissue growth. Moreover, we constructed mechanistic networks of let-7, miR-21, and miR-223, the most significantly involved upstream miRNAs. Our findings reveal that multiple upstream miRNAs (i.e., let-7, miR-21, and miR-223) were associated with gene expression changes in rat sciatic nerve stumps after nerve injury, and these miRNAs play an important role in peripheral nerve regeneration. This study was approved by the Experimental Animal Ethics Committee of Jiangsu Province of China (approval No. 20190303-18) on March 3, 2019.

Key words: bioinformatic analysis, Ingenuity Pathway Analysis, mechanistic network, microRNA, peripheral nerve injury, peripheral nerve regeneration, RNA sequencing, sciatic nerve crush