Microarray Analysis of Long Noncoding RNAs in Female Diabetic Peripheral Neuropathy Patients

Abstract

Background/Aims: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus (DM). Because of its controversial pathogenesis, DPN is still not diagnosed or managed properly in most patients. Methods: In this study, human lncRNA microarrays were used to identify the differentially expressed lncRNAs in DM and DPN patients, and some of the discovered lncRNAs were further validated in additional 78 samples by quantitative realtime PCR (qRT-PCR). Results: The microarray analysis identified 446 and 1327 differentially expressed lncRNAs in DM and DPN, respectively. The KEGG pathway analysis further revealed that the differentially expressed lncRNA-coexpressed mRNAs between DPN and DM groups were significantly enriched in the MAPK signaling pathway. The lncRNA/mRNA coexpression network indicated that BDNF and TRAF2 correlated with 6 lncRNAs. The qRT-PCR confirmed the initial microarray results. Conclusion: These findings demonstrated that the interplay between lncRNAs and mRNA may be involved in the pathogenesis of DPN, especially the neurotrophin-MAPK signaling pathway, thus providing relevant information for future studies.

Non-coding RNAs in neuropathic pain

“…lncRNAs are deregulated in diabetic peripheral neuropathy and CRPS [57,137,[174][175][176], and similar to miRNAs, they can be detected in liquid biopsies ( Table 4). The most studied lncRNA in DNP is NONRATT021972 which is up-regulated in the serum and correlates with higher neuropathic pain scores, indicating its potential as a biomarker [137,177].…”

“…Another up-regulated ncRNA in Type 2 diabetes mellitus and DNP serum is uc.48+ that is involved in purinergic receptor-mediated responses [74,178]. Amongst 1327 deregulated lncRNAs in the PBMCs of female patients with DNP, MALAT1, H19, PVT1 and MIR143HG could potentially qualify as biomarkers [174]. In female CRPS patients, XIST appears as a promising indicator of poor responsiveness to ketamine [57].…”

<p>Advances with Long Non-Coding RNAs in Diabetic Peripheral Neuropathy</p>

“…Recent studies have posited that lncRNAs may also become a significant factor in DPN. 4,5,18 One clinical study found that there were 446 and 1327 differentially expressed lncRNAs between DM and DPN patients by the microarray analysis, respectively. Although there are more and more researches on lncRNAs, the specific biological role of most lncRNAs is still unknown.…”

“…The KEGG pathway analysis of mRNAs co-expressed by differentially expressed lncRNAs between DM and DPN found that the most widely covered is the MAPK signaling pathway, which may be one of the specific mechanisms of lncRNAs participating in DPN. 4 At the same time, lncRNAs compete to occupy a large number of miRNAs in the cell, buffering and reducing their ability to interfere with the target mRNA like a sponge. Studying these ceRNA relationships has become a breakthrough for studying lncRNAs in DPN.…”

“…2,3 And some studies indicate lncRNAs may participate in the pathogenesis of diabetic peripheral neuropathy (DPN). 4,5 In this review, the latest progress of lncRNAs in DPN will be demonstrated.…”