Abstract
Background The prevalence of obesity and type 2 diabetes mellitus (T2DM) has become the most serious global public health issue. In recent years, there has been increasing attention to the role of long noncoding RNAs (lncRNAs) in the occurrence and development of obesity and T2DM. The aim of this work was to find new lncRNAs as potential predictive biomarkers or therapeutic targets for obesity and T2DM. Methods In this study, we identified significant differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) between adipose tissue of individuals with obesity and T2DM and normal adipose tissue (absolute log2FC ≥ 1 and FDR < 0.05). Then, the lncRNA-miRNA interactions predicted by miRcode were further screened with a threshold of MIC > 0.2. Simultaneously, the mRNA-miRNA interactions were explored by miRWalk 2.0. Finally, a ceRNA network consisting of lncRNAs, miRNAs, and mRNAs was established by integrating lncRNA-miRNA interactions and mRNA-miRNA interactions. Results Upon comparing adipose tissue from individuals with obesity and T2DM and normal adipose tissues, 364 significant DEmRNAs, including 140 upregulated and 224 downregulated mRNAs, were identified in GSE104674; in addition, 231 significant DEmRNAs, including 146 upregulated and 85 downregulated mRNAs, were identified in GSE133099. GO and KEGG analyses have shown that downregulated DEmRNAs in GSE104674 and GSE133099 were associated with obesity- and T2DM-related biological pathways, such as lipid metabolism, AMPK signaling, and insulin resistance. Furthermore, 28 significant DElncRNAs, including 14 upregulated and 14 downregulated lncRNAs, were found. Based on the predicted lncRNA-miRNA and mRNA-miRNA relationships, we constructed a competitive endogenous RNA (ceRNA) network, including five lncRNAs, ten miRNAs, and 15 mRNAs. KEGG-GSEA analysis revealed that four lncRNAs (FLG-AS1, SNAI3-AS1, AC008147.0, and LINC02015) in the ceRNA network were related to the biological pathways of metabolic diseases. Conclusions Through ceRNA network analysis, our study identified four new lncRNAs that may be used as potential biomarkers and therapeutic targets of obesity and T2DM, thus laying a foundation for future clinical studies.
Highlights
Obesity is a complex multifactorial disease caused by an imbalance between energy intake and consumption
A competitive endogenous RNA (ceRNA) network consisting of long noncoding RNAs (lncRNAs), miRNAs, and mRNAs was established by integrating lncRNA-miRNA interactions and mRNAmiRNA interactions
The significantly upregulated and downregulated differentially expressed mRNAs (DEmRNAs) of GSE133099 and GSE104674 were utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses
Summary
Obesity is a complex multifactorial disease caused by an imbalance between energy intake and consumption. The aim of this work was to find new lncRNAs as potential predictive biomarkers or therapeutic targets for obesity and T2DM. We identified significant differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) between adipose tissue of individuals with obesity and T2DM and normal adipose tissue (absolute log2FC ≥ 1 and FDR < 0:05). Based on the predicted lncRNA-miRNA and mRNA-miRNA relationships, we constructed a competitive endogenous RNA (ceRNA) network, including five lncRNAs, ten miRNAs, and 15 mRNAs. KEGG-GSEA analysis revealed that four lncRNAs (FLG-AS1, SNAI3-AS1, AC008147.0, and LINC02015) in the ceRNA network were related to the biological pathways of metabolic diseases. Through ceRNA network analysis, our study identified four new lncRNAs that may be used as potential biomarkers and therapeutic targets of obesity and T2DM, laying a foundation for future clinical studies
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