Association between lncRNA and GCKR gene in type 2 diabetes mellitus

Objective: To screen long non-coding RNA (lncRNA) related to glucokinase regulatory protein gene (GCKR), its differential expression was analyzed in patients with Type 2 diabetes mellitus (T2DM) and control samples. The correlation of lncRNA with GCKR was verified and its potential value as a molecular marker of T2DM was assessed. Methods: Lymphocyte RNA was extracted from five patients with T2DM and five patients with non-T2DM. The expression profiles of circulating lncRNAs and mRNAs were obtained by microarray. Bioinformatics analysis was used to screen IncRNAs associated with the GCKR gene in 127 patients with T2DM and 130 patients with non-T2DM were selected. The expression levels of the GCKR gene and IncRNA (ENST00000588707.1 and TCONS_00004187) in the T2DM group and control group were verified by real-time PCR. Additionally, a correlation analysis was conducted. The value of circulating ENST00000588707.1 and TCONS_00004187 as bio-markers for the diagnosis of T2DM was performed by receiver operating characteristic curve analysis. Results: We identified 68 IncRNAs and 74 mRNAs differentially expressed from the expression profile. Compared with the control group, the expression levels of the GCKR gene and lncRNA ENST00000588707.1 and TCONS_00004187 in the T2DM group were significantly lower (P < 0.05). The correlation analysis revealed that ENST00000588707.1 and TCONS_00004187 were correlated with GCKR gene expression and glycolipid metabolism (P < 0.05). ROC analysis showed that the area under the curve value of ENST00000588707.1 between T2DM patients and non-T2DM patients was 0.816 (95% CI: 0.764-0.869, sensitivity 72.0%, specificity 80.3%) and the AUC value of TCONS_00004187 was 0.826 (95% CI: 0.774-0.879, sensitivity 81.6%, specificity 61.3%). Conclusion: lncRNA ENST0000588707.1 and TCONS00004187 could serve as potential biomarkers for T2DM, which could involve in glycolipid metabolism by regulating the GCKR gene.