Abstract
BackgroundType 2 diabetes mellitus (T2DM) is mainly affected by genetic and environmental factors; however, the correlation of long noncoding RNAs (lncRNAs) with T2DM remains largely unknown.MethodsMicroarray analysis was performed to identify the differentially expressed lncRNAs and messenger RNAs (mRNAs) in patients with T2DM and healthy controls, and the expression of two candidate lncRNAs (lnc-HIST1H2AG-6 and lnc-AIM1-3) were further validated using quantitative real-time polymerase chain reaction (qRT-PCR). Spearman’s rank correlation coefficient was used to measure the degree of association between the two candidate lncRNAs and differentially expressed mRNAs. Furthermore, the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway and GO (Gene Ontology) enrichment analysis were used to reveal the biological functions of the two candidate lncRNAs. Additionally, multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed.ResultsThe microarray analysis revealed that there were 55 lncRNAs and 36 mRNAs differentially expressed in patients with T2DM compared with healthy controls. Notably, lnc-HIST1H2AG-6 was significantly upregulated and lnc-AIM1-3 was significantly downregulated in patients with T2DM, which was validated in a large-scale qRT-PCR examination (90 controls and 100 patients with T2DM). Spearman’s rank correlation coefficient revealed that both lncRNAs were correlated with 36 differentially expressed mRNAs. Furthermore, functional enrichment (KEGG and GO) analysis demonstrated that the two lncRNA-related mRNAs might be involved in multiple biological functions, including cell programmed death, negative regulation of insulin receptor signal, and starch and sucrose metabolism. Multivariate logistic regression analysis revealed that lnc-HIST1H2AG-6 and lnc-AIM1-3 were significantly correlated with T2DM (OR = 5.791 and 0.071, respectively, both P = 0.000). Furthermore, the ROC curve showed that the expression of lnc-HIST1H2AG-6 and lnc-AIM1-3 might be used to differentiate patients with T2DM from healthy controls (area under the ROC curve = 0.664 and 0.769, respectively).ConclusionThe profiles of lncRNA and mRNA were significantly changed in patients with T2DM. The expression levels of lnc-HIST1H2AG-6 and lnc-AIM1-3 genes were significantly correlated with some features of T2DM, which may be used to distinguish patients with T2DM from healthy controls and may serve as potential novel biomarkers for diagnosis in the future.
Highlights
Type 2 diabetes mellitus (T2DM) is mainly affected by genetic and environmental factors; the correlation of long noncoding RNAs with T2DM remains largely unknown
The Body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FPG), HbA1c, fasting insulin (FIN), HOMA-insulin resistance (IR), HOMA-B, Low-density lipoprotein cholesterol (LDL-C), and High-density lipoprotein cholesterol (HDL-C) of patients with T2DM were significantly different from those of healthy controls (P < 0.05 or P < 0.01), indicating that these blood samples from the subjects described above could be used for the following experimental analysis
Expression profile of long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) by microarray analysis In the present study, we compared the gene expression profile displayed by peripheral blood mononuclear cells (PBMCs) from patients with T2DM with that of healthy controls by using the GeneSpring Software
Summary
Type 2 diabetes mellitus (T2DM) is mainly affected by genetic and environmental factors; the correlation of long noncoding RNAs (lncRNAs) with T2DM remains largely unknown. Diabetes mellitus (DM), one of the most common chronic diseases worldwide, is characterized by elevated blood glucose levels. T2DM has become an important public health problem that has serious effects on quality of life due to chronic complications, including nephropathies, retinopathies, neuropathies, and cardiovascular diseases [4]. In previous decades, noncoding RNAs (ncRNAs), involving microRNAs, small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and piwi-interacting RNAs (piRNAs) have been the focus of research because of their important biological functions that are strongly associated with the occurrence and development of many diseases, including T2DM [5, 6]
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