Abstract
Objective Long noncoding RNA (lncRNA) and circular RNA (circRNA) are receiving increasing attention in diabetes research. However, there are still many unknown lncRNAs and circRNAs that need further study. The aim of this study is to identify new lncRNAs and circRNAs and their potential biological functions in type 2 diabetes mellitus (T2DM). Methods RNA sequencing and differential expression analysis were used to identify the noncoding RNAs (ncRNAs) and mRNAs that were expressed abnormally between the T2DM and control groups. The competitive endogenous RNA (ceRNA) regulatory network revealed the mechanism of lncRNA and circRNA coregulating gene expression. The biological functions of lncRNA and circRNA were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The candidate hub mRNAs were selected by the protein-protein interaction (PPI) network and validated by using the Gene Expression Omnibus (GEO) database. Results Differential expression analysis results showed that 441 lncRNAs (366 upregulated and 75 downregulated), 683 circRNAs (354 upregulated and 329 downregulated), 93 miRNAs (63 upregulated and 30 downregulated), and 2923 mRNAs (1156 upregulated and 1779 downregulated) were identified as remarkably differentially expressed in the T2DM group. The ceRNA regulatory network showed that a single lncRNA and circRNA can be associated with multiple miRNAs, and then, they coregulate more mRNAs. Functional analysis showed that differentially expressed lncRNA (DElncRNA) and differentially expressed circRNA (DEcircRNA) may play important roles in the mTOR signaling pathway, lysosomal pathway, apoptosis pathway, and tuberculosis pathway. In addition, PIK3R5, AKT2, and CLTA were hub mRNAs screened out that were enriched in an important pathway by establishing the PPI network. Conclusions This study is the first study to explore the molecular mechanisms of lncRNA and circRNA in T2DM through the ceRNA network cofounded by lncRNA and circRNA. Our study provides a novel insight into the T2DM from the ceRNA regulatory network.
Highlights
Type 2 diabetes mellitus (T2DM), formerly known as adultonset diabetes, is a kind of non-insulin-dependent diabetes, which was one of the most common chronic diseases in the population [1]
To explore the function of noncoding RNAs (ncRNAs) in T2DM, we investigated the differential expression of Long noncoding RNA (lncRNA) (DElncRNA), circular RNA (circRNA) (DEcircRNA), miRNA (DEmiRNA), and mRNA (DEmRNA) by high-throughput sequencing
Some studies found that the dysregulated expression of lncRNA or circRNA was related to the occurrence and development of diabetes mellitus, such as XLOC010971, XLOC-013310 [19], and miR-7 [20]
Summary
Type 2 diabetes mellitus (T2DM), formerly known as adultonset diabetes, is a kind of non-insulin-dependent diabetes, which was one of the most common chronic diseases in the population [1]. The global prevalence of adult diabetes and impaired glucose tolerance has been increasing in recent decades [2,3,4]. According to the IDF Diabetes Atlas, 451 million people (aged 18 to 99 years) worldwide suffered from diabetes in 2017, and the records were predicted to augment to 693 million by 2045 [5]. The global cost of diabetes was reported to be $13100 (95% CI: 1.28-1.36) or 1.8% (95% CI: 1.8-1.9) of global gross domestic product (GDP) [6]. The occurrence and development of T2DM were mainly related to the environment and heredity. The results of the epidemiological investigation showed that obesity, high-calorie diet, and lack of physical activity were the most important
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