High-Throughput Sequencing and Exploration of the lncRNA-circRNA-miRNA-mRNA Network in Type 2 Diabetes Mellitus

Author:

Yang Fang1ORCID,Chen Yang2ORCID,Xue Zhiqiang3ORCID,Lv Yaogai2ORCID,Shen Li4ORCID,Li Kexin2ORCID,Zheng Pingping2ORCID,Pan Pan2ORCID,Feng Tianyu2,Jin Lina2ORCID,Yao Yan2ORCID

Affiliation:

1. Department of Health Management Center, the First Hospital of Jilin University, Jilin University, Changchun, Jilin, 130021, China

2. Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin, 130021, China

3. Department of Epidemiology and Statistics, School of Public Health, Xinjiang Medical University, Urumqi, 830011, China

4. Department of Hospital Infection Management, Zhengzhou People’s Hospital, Zhengzhou, Henan, 450000, China

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.

Funder

Science and Technology Development Plan Project of Jilin Province

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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