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

BMC Medical Genomics

Chenguang Wu¹  Hui Jiang¹  Xiaoluo Chen¹  Shihe Shao²  Peian Lou³ 

[1] Department of Endocrinology, Affiliated People’s Hospital of Jiangsu University, 212002, Zhenjiang, China;School of Medicine, Jiangsu University, 301 Xuefu Road, 212013, Zhenjiang, Jiangsu Province, China;Xuzhou Center for Disease Control Prevention, 221000, Xuzhou, China;

关键词: Long noncoding RNA;    Type 2 diabetes mellitus;    Gene expression;    Microarray analysis;    Lnc-HIST1H2AG-6;    Lnc-AIM1-3;   

DOI  :  10.1186/s12920-021-00994-z

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY