Deregulation of lncRNA HIST1H2AG-6 and AIM1-3 in peripheral blood mononuclear cells is associated with newly diagnosed type 2 diabetes

Abstract

Background Type 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. Methods Microarray 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. Results The 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). Conclusion The 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.

Unveiling The Role of lncRNA NRON and NFATc3 In Type 2 Diabetes Mellitus: A Molecular Insight for Disease Pathogenesis and Biomarker Discovery

“…and lnc-AIM1-3) and the levels of FIN, FPG, HOMA-B and HbA1c-B [30]. In addition, a negatively correlation was observed between NFATc3 expression and HbA1c, FPG.…”

Analysis and validation of biomarkers of immune cell-related genes in postmenopausal osteoporosis: An observational study

“…The expression level of lnc-HIST1H2AG-6 gene were significantly correlated with some features of T2DM. [18] High expression of LYPLA1 was associated with a poor prognosis in lung adenocarcinoma (LUAD). [60] In this study, in order to explore the functional annotations of 5 signature genes, the GSEA analysis found that they were associated with immune macromolecules such as proteasome, mitochondria and lysosome.…”

“…The expression level of lnc-HIST1H2AG-6 gene were significantly correlated with some features of T2DM. [ 18 ] High expression of LYPLA1 was associated with a poor prognosis in lung adenocarcinoma (LUAD). [ 60 ]…”

“…A Wilcoxon rank sum test was used to compare the differences between low BMD and high BMD for different immune cells in the combined dataset, and box plots were drawn using the ggpubr package (version 0.4.0) to visualize the comparative results. [ 18 ]…”