Long non‐coding RNA screening and identification of potential biomarkers for type 2 diabetes

• Published in: Journal of clinical laboratory analysis 2022-04, Vol.36 (4), p.e24280-n/a
• Main Authors: Ma, Qi, Wang, Li, Wang, Zhiqiang, Su, Yinxia, Hou, Qinqin, Xu, Qiushuang, Cai, Ren, Wang, Tingting, Gong, Xueli, Yi, Qizhong
• Format: Article
• Language: English
• Subjects: Bioinformatics; biological markers; Biomarkers; Cardiovascular disease; Chronic illnesses; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - genetics; DNA microarrays; Ethnicity; expression regulation; Gene expression; Gene Expression Profiling; Genetic screening; Glucose; Glucose metabolism; Han Han; Humans; Lipid metabolism; lncRNA; Medical diagnosis; microarray analysis; Non-coding RNA; Plasma; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Messenger - genetics; Software; Transcriptomes; type 2 diabetes
• ISSN: 0887-8013; 1098-2825
• DOI: 10.1002/jcla.24280

Background To investigate new lncRNAs as molecular markers of T2D. Methods We used microarrays to identify differentially expressed lncRNAs and mRNAs from five patients with T2D and paired controls. Through bioinformatics analysis, qRT‐PCR validation, ELISA, and receiver operating characteristic (ROC) curve analysis of 100 patients with T2D and 100 controls to evaluate the correlation between lncRNAs and T2D, and whether lncRNAs could be used in the diagnosis of T2D patients. Results We identified 68 and 74 differentially expressed lncRNAs and mRNAs, respectively. The top five upregulated lncRNAs are ENST00000381108.3, ENST00000515544.1, ENST00000539543.1, ENST00000508174.1, and ENST00000564527.1, and the top five downregulated lncRNAs are TCONS_00017539, ENST00000430816.1, ENST00000533203.1, ENST00000609522.1, and ENST00000417079.1. The top five upregulated mRNAs are Q59H50, CYP27A1, DNASE1L3, GRIP2, and lnc‐TMEM18‐12, and the top five downregulated mRNAs are GSTM4, PODN, GLYATL2, ZNF772, and CLTC. Examination of lncRNA‐mRNA interaction pairs indicated that the target gene of lncRNA XR_108954.2 is E2F2. Multiple linear regression analysis showed that XR_108954.2 (r = 0.387, p < 0.01) and E2F2 (r = 0.368, p < 0.01) expression levels were positively correlated with glucose metabolism indicators. Moreover, E2F2 was positively correlated with lipid metabolism indicators (r = 0.333, p < 0.05). The area under the ROC curve was 0.704 (95% CI: 0.578–0.830, p = 0.05) for lncRNA XR_108954.2 and 0.653 (95% CI: 0.516–0.790, p = 0.035) for E2F2. Conclusions This transcriptome analysis explored the aberrantly expressed lncRNAs and identified E2F2 and lncRNA XR_108954.2 as potential biomarkers for patients with T2D. Scatter plot analysis of lncRNAs (A) and mRNAs (B) expression. We identified differentially expressed 68 lncRNAs from the peripheral blood cells (44 up‐regulated and 24 down‐regulated) and 74 differentially expressed mRNAs (56 up‐regulated and 18 down‐regulated).