Comprehensive analysis of differentially expressed microRNAs and mRNAs in dorsal root ganglia from streptozotocin-induced diabetic rats

Abstract

Diabetic peripheral neuropathy is a common complication associated with diabetes mellitus with a pathogenesis that is incompletely understood. By regulating RNA silencing and post-transcriptional gene expression, microRNAs participate in various biological processes and human diseases. However, the relationship between microRNAs and the progress of diabetic peripheral neuropathy still lacks a thorough exploration. Here we used microarray microRNA and mRNA expression profiling to analyze the microRNAs and mRNAs which are aberrantly expressed in dorsal root ganglia from streptozotocin-induced diabetic rats. We found that 37 microRNAs and 1357 mRNAs were differentially expressed in comparison to non-diabetic samples. Bioinformatics analysis indicated that 399 gene ontology terms and 29 Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched in diabetic rats. Additionally, a microRNA-gene network evaluation identified rno-miR-330-5p, rno-miR-17-1-3p and rno-miR-346 as important players for network regulation. Finally, quantitative real-time polymerase chain reaction analysis was used to confirm the microarray results. In conclusion, this study provides a systematic perspective of microRNA and mRNA expression in dorsal root ganglia from diabetic rats, and suggests that dysregulated microRNAs and mRNAs may be important promotors of peripheral neuropathy. Our results may be the underlying framework of future studies regarding the effect of the aberrantly expressed genes on the pathophysiology of diabetic peripheral neuropathy.

The circ_0002538/miR-138-5p/PLLP axis regulates Schwann cell migration and myelination in diabetic peripheral neuropathy

“…The copyright holder for this preprint this version posted February 25, 2022. ; https://doi.org/10.1101/2022.02.24.481714 doi: bioRxiv preprint between patients with static or progressive diabetic neuropathy that are functionally enriched in pathways including the regulation of axonogenesis and lipid metabolism (Hur et al, 2011). A microarray analysis of the DRG of diabetic rats found that DEmRNAs with downregulated expression were significantly enriched in various biological processes, including myelination, peripheral nervous system myelination, axon guidance and regulation of axon production (Guo et al, 2018).…”

“…Previous research has identified hundreds of differentially expressed genes between patients with static or progressive diabetic neuropathy that are functionally enriched in pathways including the regulation of axonogenesis and lipid metabolism(Hur et al, 2011). A microarray analysis of the DRG of diabetic rats found that DEmRNAs with downregulated expression were significantly enriched in various biological processes, including myelination, peripheral nervous system myelination, axon guidance and regulation of axon production(Guo et al, 2018). Aberrantly expressed mRNAs in SCs isolated from the sciatic nerve of diabetic rats were enriched in downregulated biological processes related to myelination, axonogenesis and axon development(Wang et al, 2020b).…”

Emerging Roles of microRNAs as Biomarkers and Therapeutic Targets for Diabetic Neuropathy

“…Guo et al examined microRNA and mRNA expression profiling in the dorsal root ganglia isolated from diabetic rats and built a microRNA-gene network. They found that miR-17-1-3p, miR-330-5p, and miR-346 are potent promoters of DN (113). Xourgia et al proposed that miR-146, miR-499a, and miR-199a-3p are possible biomarkers of DN (21).…”

Insights into the Role of MicroRNAs in the Onset and Development of Diabetic Neuropathy

“…In another microarray analysis of miRNAs in DRG tissues of DPN rats, 37 miRNAs were differentially expressed in the diabetic group. Specifically, 15 and 22 miRNAs were upregulated or downregulated, respectively [60]. In particular, using a miRanda database, 10,011 predicted target genes were found from the 37 dysregulated miRNAs; a miRNA-gene-network analysis revealed that among these miRNAs, miR-330-5p, miR-17-1- 3p, and miR-346 had a high degree of correlation [60].…”

“…Specifically, 15 and 22 miRNAs were upregulated or downregulated, respectively [60]. In particular, using a miRanda database, 10,011 predicted target genes were found from the 37 dysregulated miRNAs; a miRNA-gene-network analysis revealed that among these miRNAs, miR-330-5p, miR-17-1- 3p, and miR-346 had a high degree of correlation [60]. Meanwhile, podocalyxin-like (Podxl, inhibiting cell-cell adhesion) and homeobox A1 (Hoxa1, sequence specific transcription factor) were the most common target mRNAs with the highest degrees of connectivity [60].…”