Differential Expression of lncRNA-miRNA-mRNA and Their Related Functional Networks in New-Onset Type 2 Diabetes Mellitus among Chinese Rural Adults

Abstract

Increasing evidence suggested that the expression and inter-regulation of long noncoding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) were related to the development of diabetes. Based on bioinformatics analysis, this study aimed to comprehensively analyze the dysregulated RNA molecules related to new-onset type 2 diabetes mellitus (T2DM). Twenty-four patients with new-onset T2DM were included as cases, and sex- and age-matched participants were included as controls. The differentially expressed lncRNAs, miRNAs, and mRNAs between the two groups were screened by RNA sequencing. LncRNA-miRNA-mRNA network and enrichment analysis were used to reveal the RNA molecules that were potentially associated with T2DM and their early changes. A total of 123 lncRNAs, 49 miRNAs, and 312 mRNAs were differentially expressed in the new-onset T2DM (fold change ≥ 1.5 and p value < 0.05). Functional analysis revealed that differentially expressed RNAs were likely to play essential roles in diabetes-related pathways. In addition, the protein–protein interaction (PPI) network screened multiple hub mRNAs, and lncRNA-miRNA-mRNA networks showed that a single miRNA could be related to multiple lncRNAs, and then they coregulated more mRNAs. SLC25A4, PLCB1, AGTR2, PRKN, and SCD5 were shown to be important mRNAs in T2DM, and miR-199b-5p, miR-202-5p, miR-548o-3p as well as miR-1255b-5p could be involved in their regulation. In conclusion, several new and previously identified dysregulated lncRNAs, miRNAs, and mRNAs were found to be vital biomarkers in T2DM. Their alterations and interactions could modulate the pathophysiology of T2DM. Those findings may provide new insights into the molecular mechanisms underlying the development of T2DM.

LINC01137/miR-186-5p/WWOX: a novel axis identified from WWOX-related RNA interactome in bladder cancer

“…Moreover, LINC01063 and SNED1-AS1 were not a part of the interconnected network visualized in Figure 3A and had noticeably worse AvgRank values than HIPK1-AS1 and LINC01137 . Increased expression of LINC01137 during WWOX overexpression suggests that LINC01137 might be able to unravel a direct WWOX-containing lncRNA/miRNA/mRNA axis ( Figure 3E ) because the expression of lncRNA and mRNA in such axes is oftentimes positively correlated ( Pacholewska and Sung, 2019 ; Song et al, 2022 ). In summary, LINC01137 was selected as the most relevant gene because a) it was a part of the interconnected network, b) it had been ranked as one of the best genes according to mSVM-RFE, c) its expression change between cellular variants was statistically significant, and d) it was increased in WWOX-overexpressing variants so that it might be able to unravel a direct WWOX-containing lncRNA/miRNA/mRNA axis.…”

Gene expression analysis reveals diabetes-related gene signatures

“…The expression of genes and proteins can also be regulated post-transcriptionally by noncoding RNAs, such as lncRNAs and miRNAs. Both lncRNAs and miRNAs have been shown to execute vital roles in the regulation of diabetes pathophysiological processes [ 7 ].…”

“…MiRNAs are highly stable and can be found in several tissues and body fluids, including human peripheral blood, suggesting that they can be a source of accessible biomarkers of the disease [ 7 ]. Over the years, an increasing number of miRNAs have been associated with diabetes pathogenesis.…”

“…Each of these levels can be modulated by different elements causing alterations in cell function [ 6 ]. MiRNAs and lncRNAs are single-stranded RNA molecules of approximately 22 and more than 200 nucleotides in length, respectively [ 7 ]. They are involved in the regulation of different processes, including the cell cycle and cellular differentiation, with possible roles in multiple physiological and pathological processes, such as cell interactions, immune responses, and other cellular functions, via post-translational modifications.…”

Molecular Basis of Unequal Alternative Splicing of Human SCD5 and Its Alteration by Natural Genetic Variations

“…In recent years, the results of high-throughput whole genome, transcriptome and microRNA sequencing data have directed attention to tumor-related changes in the expression level of SCD5 [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ]; however, the underlying molecular mechanism of these alterations remains to be elucidated. Currently, SCD5 is primarily considered a promising type-specific tumor marker.…”