Integrated analysis of microRNA and mRNA expression profiles in the rat spinal cord under inflammatory pain conditions

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.

Circ_0038467 regulates lipopolysaccharide‐induced inflammatory injury in human bronchial epithelial cells through sponging miR‐338‐3p

“…Until now, many miRNAs, such as miR‐1247 and miR‐3941 have been reported to regulate LPS‐induced inflammatory damage in acute pneumonia . Previous evidence described that miR‐338‐3p was involved in the inflammatory damage in the rat spinal cord . Additionally, miR‐338‐3p was reported to weaken TNF‐α‐induced lipogenesis in sebocytes .…”

Integrated analysis of Transcriptomic Data Reveal AP-1 as a Potential Regulation Hub in Inflammation Induced Hyperalgesia Rat

“…Although only an array-based analysis focused on microRNA (miRNA) and mRNA network was used, they were still able to reveal that several miRNA-mRNA interactions contributed to the in ammatory pain process. For instance, they found that miR-124-3p could attenuate in ammatory pain and decrease IL-6R expression in the spinal cord [17]. Aside from this study, miRNAs have already been widely associated with in ammatory models [1; 12; 27; 33].…”

Integrated analysis of Transcriptomic Data Reveal AP-1 as a Potential Regulation Hub in Inflammation Induced Hyperalgesia Rat

“…Interestingly, most of the differentially expressed miRNAs (104/120) were downregulated after CFA treatment. The global downregulation of miRNA itself is an interesting phenomenon, which was missed in the previous arraybased study [17]. Notably, in these downregulated miRNAs, many of them are targeting AP-1 network genes.…”

“…These studies suggested that epigenetic regulation, especially DNA methylation could contribute to in ammatory pain. In addition, although Tan et al provided rat SDH tissue expression pro les days after CFA treatment using microarray technology [17], the transcriptomic pro le of the dorsal root ganglion (DRG) tissues from the chronic pain animal models is still lacking. This suggested that how the gene expression is affected by CFA treatment in the primary sensory neurons is still not clear.…”