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

Author:

Song Yu,Nie Luting,Wang Mian,Liao Wei,Huan Changsheng,Jia Zexin,Wei Dandan,Liu Pengling,Fan Keliang,Mao Zhenxing,Wang ChongjianORCID,Huo WenqianORCID

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.

Funder

the National Key Research and Development Program of China

the Postdoctoral Science Foundation of China

the National Natural Science Foundation of China

Henan Science and Technology Development Program

the Scientific and Technological Innovation of Colleges and Universities in Henan Province Talent Support Programme

the Excellent Youth Development Foundation of Zhengzhou University

the Young Backbone Teachers Program of Colleges and Universities in Henan Province

Publisher

MDPI AG

Subject

Genetics (clinical),Genetics

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