Dataset Information

Network Analysis of miRNA and mRNA Changes in the Prelimbic Cortex of Rats With Chronic Neuropathic Pain: Pointing to Inflammation.

ABSTRACT: Neuropathic pain (NP) is a complex, chronic pain condition caused by injury or dysfunction affecting the somatosensory nervous system. This study aimed to identify crucial mRNAs and microRNAs (miRNAs) in the prelimbic cortex (PL) of NP rats. mRNA and miRNA microarrays were applied in the present study. The miRNA-mRNA regulatory network was constructed by using ingenuity pathway analysis (IPA). A total of 35 differentially expressed (DE) RNAs (24 miRNAs and 10 mRNAs) were identified in the spared nerve injury (SNI) group compared with the control group. The DE miRNA-mRNA network showed that IL-6 and tumor necrosis factor (TNF) were core components. Mir-30c-5p and mir-16-5p were the most connected miRNAs in the network. Interestingly, four mRNAs (Rnase 4, Egr2, Rexo4, and Klf2) with significantly increased expression were abundantly expressed in microglia, which was verified by the real-time quantitative polymerase chain reaction (qPCR). Furthermore, the expression of Rnase4 and Egr2 decreased in M1-polarized macrophages and increased in M2-polarized macrophages. In conclusion, we screened dozens of DE mRNAs and miRNAs in the PL of SNI rats. The core of the DE mRNA and miRNA network pointed to molecules associated with inflammation. Four mRNAs (Rnase4, Egr2, Rexo4, and Klf2) might be the potential markers of M2 polarization.

SUBMITTER: Cai G

PROVIDER: S-EPMC7324672 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Network Analysis of miRNA and mRNA Changes in the Prelimbic Cortex of Rats With Chronic Neuropathic Pain: Pointing to Inflammation.

Cai Guohong G Zhu Yuanyuan Y Zhao Yan Y Chen Jing J Guo Chihua C Wu Feifei F Huang Jing J Wu Shengxi S

Frontiers in genetics 20200623

Neuropathic pain (NP) is a complex, chronic pain condition caused by injury or dysfunction affecting the somatosensory nervous system. This study aimed to identify crucial mRNAs and microRNAs (miRNAs) in the prelimbic cortex (PL) of NP rats. mRNA and miRNA microarrays were applied in the present study. The miRNA-mRNA regulatory network was constructed by using ingenuity pathway analysis (IPA). A total of 35 differentially expressed (DE) RNAs (24 miRNAs and 10 mRNAs) were identified in the spared ...[more]

PMID: 32655622

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Project description:BackgroundNeuropathic pain (NP) takes a heavy toll on individual life quality, yet gaps in its molecular characterization persist and effective therapy is lacking. This study aimed to provide comprehensive knowledge by combining transcriptomic and proteomic data of molecular correlates of NP in the anterior cingulate cortex (ACC), a cortical hub responsible for affective pain processing.MethodsThe NP model was established by spared nerve injury (SNI) in Sprague-Dawley rats. RNA sequencing and proteomic data from the ACC tissue isolated from sham and SNI rats 2 weeks after surgery were integrated to compare their gene and protein expression profiles. Bioinformatic analyses were performed to figure out the functions and signaling pathways of the differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) enriched in.ResultsTranscriptomic analysis identified a total of 788 DEGs (with 49 genes upregulated) after SNI surgery, while proteomic analysis found 222 DEPs (with 89 proteins upregulated). While Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of the DEGs suggested that most of the altered genes were involved in synaptic transmission and plasticity, bioinformatics analysis of the DEPs revealed novel critical pathways associated with autophagy, mitophagy, and peroxisome. Notably, we noticed functionally important NP-related changes in the protein that occurred in the absence of corresponding changes at the level of transcription. Venn diagram analysis of the transcriptomic and proteomic data identified 10 overlapping targets, among which only three genes (XK-related protein 4, NIPA-like domain-containing 3, and homeodomain-interacting protein kinase 3) showed concordance in the directions of change and strong correlations between mRNA and protein levels.ConclusionThe present study identified novel pathways in the ACC in addition to confirming previously reported mechanisms for NP etiology, and provided novel mechanistic insights for future research on NP treatment. These findings also imply that mRNA profiling alone fails to provide a complete landscape of molecular pain in the ACC. Therefore, explorations of changes at the level of protein are necessary to understand NP processes that are not transcriptionally modulated.

Dataset Information

Network Analysis of miRNA and mRNA Changes in the Prelimbic Cortex of Rats With Chronic Neuropathic Pain: Pointing to Inflammation.

Publications

Network Analysis of miRNA and mRNA Changes in the Prelimbic Cortex of Rats With Chronic Neuropathic Pain: Pointing to Inflammation.

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