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Published on: May 4, 2021
Integrated analysis of microRNA and mRNA expression profiles in the rat spinal cord under inflammatory pain
Chien Cheng Liu1,2, Jiin Tsuey Cheng1, Tien Yui Li2
1Department of Biological Sciences, National Sun Yat-sen University, No. 70, Lienhai Rd., Gushan Dist., Kaohsiung City, 80424, Taiwan.
Abstract:
Recent studies using microarray-based approaches have demonstrated that microRNAs (miRNAs) are involved in pain processing pathways. However, a significant proportion of computational predictions of miRNA targets are false-positive interactions. To increase the chance of identifying biologically relevant targets, we performed an integrated analysis of both miRNA and mRNA expression profiles in the rat spinal cord during complete Freund's adjuvant (CFA)-induced inflammatory pain. We generated miRNA and mRNA arrays from the same corresponding samples on days 5 and 14 after CFA injection. Five miRNAs and 1096 mRNAs in the CFA 5d group and 16 miRNAs and 647 mRNAs in the CFA 14d group were differentially expressed based on a filter of at least a 1.5-fold change in either direction. An integrated analysis revealed 54 mRNA targets with an inverse correlation to the expression patterns of three miRNAs in the CFA 5d group. Seventy-five targets were inversely correlated to six miRNAs in the CFA 14d group. The miRNA-mRNA interaction networks revealed significant changes in miR-124, miR-149, miR-3584 and their target genes, IL-6R, ADAM19, LAMC1 and CERS2, in the CFA 5d group. In the CFA 14d group, significant changes were noted in miR-124, miR-29, miR-34, miR-30, miR-338 and their target genes, TIMP2, CREB5 and EFNB1. We also investigated an interaction pair, miR-124-3p and IL-6R, and the results showed that miR-124-3p could attenuate inflammatory pain and decrease IL-6R expression in the spinal cord. These specific miRNAs and their target genes provide possible avenues for the diagnosis and treatment of inflammatory pain.
Insights
This study identifies specific microRNAs (miRNAs) and their target genes involved in inflammatory pain pathways. These findings offer potential new diagnostic and therapeutic targets for pain management.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are implicated in pain processing, but target prediction accuracy is limited.
- Computational miRNA target predictions often yield false positives, necessitating experimental validation.
Purpose of the Study:
- To identify biologically relevant miRNA-mRNA interactions in the rat spinal cord during inflammatory pain.
- To elucidate the role of specific miRNAs and their targets in the development and progression of inflammatory pain.
Main Methods:
- Integrated analysis of miRNA and mRNA expression profiles from rat spinal cords at 5 and 14 days post-CFA injection.
- Differential expression analysis and correlation analysis to identify inversely expressed miRNA-mRNA pairs.
- Construction of miRNA-mRNA interaction networks.
Main Results:
- Significant differential expression of miRNAs and mRNAs observed at both 5 and 14 days post-CFA injection.
- Identification of 54 and 75 miRNA-mRNA targets in the early and later stages, respectively.
- Key miRNA-mRNA interactions involving miR-124, miR-149, miR-3584, and targets like IL-6R, ADAM19, LAMC1, CERS2 were highlighted. miR-124-3p demonstrated a role in attenuating inflammatory pain and reducing IL-6R expression.
Conclusions:
- Specific miRNAs, including miR-124, and their target genes, such as IL-6R, are critical players in inflammatory pain.
- These identified miRNA-target interactions represent promising candidates for novel diagnostic markers and therapeutic interventions for inflammatory pain.
