The Differential Expression of Long Noncoding RNAs in Type 2 Diabetes Mellitus and Latent Autoimmune Diabetes in Adults

Abstract

Background. Long noncoding RNAs (lncRNAs) were previously found to be closely related to the pathogenesis of diabetes. Objectives. To reveal the differentially expressed lncRNAs and messenger RNAs (mRNAs) involved in type 2 diabetes mellitus (T2DM) and latent autoimmune diabetes in adults (LADA) and predict the lncRNA target genes to derive their expression profiles for the diagnosis of T2DM and LADA and their differential diagnosis. Methods. Twelve venous blood samples were collected from T2DM patients, LADA patients, and nondiseased subjects to obtain total RNAs. After removing rRNA from total RNAs to establish the desired library for sequencing, quality control and quantification analyses were carried out. The fragments per kilobase of exon model per million reads mapped (FPKM) of lncRNAs were calculated to construct the gene expression profiles of lncRNAs and mRNAs. Fold changes (fold change: 2.0) and p values (p value: 0.05, FPKM ≥ 0.1) were calculated, and then differentially expressed lncRNAs and mRNAs were screened. To obtain the significantly coexpressed lncRNA-mRNA pairs, the lncRNA target genes were deduced according to the association between adjacent sites. Results. Compared to nondiseased controls, 68,763 versus 28,523 lncRNAs and 133 versus 1035 mRNAs were significantly upregulated and significantly downregulated, respectively, in T2DM patients. For LADA patients, 68,748 versus 28,538 lncRNAs and 219 versus 805 mRNAs were significantly upregulated and significantly downregulated, respectively, relative to nondiseased controls. Compared to T2DM patients, 74,207 versus 23,079 lncRNAs and 349 versus 137 mRNAs were significantly upregulated and significantly downregulated, respectively, in LADA patients. Based on the correlation analysis, seven lncRNA-mRNA pairs (BTG2, A2M, HECTD4, MBTPS1, DBH, FLVCR1, and NCBP2) were significantly coexpressed, and two lncRNAs (ENST00000608916 and ENST00000436373) were newly discovered. Conclusion. Significant differences in lncRNA expression were discovered among the three groups. Furthermore, after predicting lncRNA expression profiles, GO/KEGG pathway analysis could deduce the target gene function.