Abstract
Peripheral nerve injury is a worldwide clinical issue that impacts patients’ quality of life and causes huge society and economic burden. Injured peripheral nerves are able to regenerate by themselves. However, for severe peripheral nerve injury, the regenerative abilities are very limited and the regenerative effects are very poor. A better understanding of the mechanisms following peripheral nerve injury will benefit its clinical treatment. In this study, we systematically explored the dynamic changes of mRNAs and long non-coding RNAs (lncRNAs) in the injured sciatic nerve segments after nerve crush, identified significantly involved Gene ontology (GO) terms and Kyoto Enrichment of Genes and Genomes (KEGG) pathways, and innovatively analyzed the correlation of differentially expressed mRNAs and lncRNAs. After the clustering of co-expressed mRNAs and lncRNAs, we performed functional analysis, selected GO term “negative regulation of cell proliferation”, and constructed a competing endogenous RNA (ceRNA) network of LIF and HMOX1 gene in this GO term. This study is the first to provide a systematic dissection of mRNA-microRNA (miRNA)-lncRNA ceRNA network following peripheral nerve injury and thus lays a foundation for further investigations of the regulating mechanisms of non-coding RNAs in peripheral nerve repair and regeneration.
Highlights
Peripheral nerve injury, resulting from a variety of different reasons such as mechanical compression, ischemia, penetrating injury, stretch injury, and cold injury, may seriously affect patients’ quality of life and cause huge society and economic burden [1]
Besides a deeper investigation of differentially expressed mRNAs, we identified differentially expressed Long non-coding RNA (lncRNA), combined differentially expressed lncRNAs with differentially expressed mRNAs, and constructed correlated competing endogenous RNA networks of Leukemia inhibitory factor (LIF) gene and Heme oxygenase 1 (HMOX1) gene based on miRWalk-validated miRNA-mRNA interaction and TargetScan-predicted miRNA-lncRNA interaction
A full list of all significantly differentially expressed mRNAs and lncRNAs were shown in Additional file 2: Table S2
Summary
Peripheral nerve injury, resulting from a variety of different reasons such as mechanical compression, ischemia, penetrating injury, stretch injury, and cold injury, may seriously affect patients’ quality of life and cause huge society and economic burden [1]. It is reported that peripheral nerve injury affects about 1.5–2.8% of trauma patients and often leads to life-long morbidity and disability [2, 3]. In the United States, about 360,000 patients are suffering from upper extremity paralytic syndromes annually and more than $150 billion is used to treat peripheral nerve injury every year [4, 5]. High-throughput screenings, such as microarrays and sequencing, are advanced large scale technologies for genome-wide analysis. Sequencing directly detects transcripts and has many advantages such as low background noise, large dynamic range, and high reproducibility [8, 9]. Besides the systematic identification of expressed profiles of known mRNAs, the application of sequencing benefits the identifications of unannotated transcripts and non-coding RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs
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