Expression pattern of long noncoding RNA Dancr in gluconeogenesis related models and potential regulatory association with gluconeogenesis

Abstract

Objective To explore the spatiotemporal expression of the long non-coding RNA (lncRNA) Dancr in liver, and further investigate its regulatory relationships and molecular mechanisms with hepatic gluconeogenesis. Methods Fasting-refeeding and high fat diet (HFD) induced obesity models were built, and the expression levels of Dancr in both models were detected with phosphoenolpyruvate carboxykinase and glucose-6-phosphatase (as positive control group). The expressions of Dancr were also detected in different tissues. The characteristics of Dancr and interactive miRNAs were analyzed by using online databases of NCBI, UCSC, RegRNA, TargetScan, etc. The miRNA target genes of gene ontology, kyoto encyclopedia of genes and genomes enrichment analyses were also preformed. Analysis of variance and student-t were used for comparison in multiple groups. Results The expression of Dancr was significantly increased during fasting and reached to peak after fasting for 16 h, and then returned back to normal rapidly after refeeding (1.00±0.23 vs. 4.20±0.27, t=22.10, P<0.01). Moreover, levels of Dancr expression were significantly increased in HFD induced obese mice liver models than those in normal controls (1.00±0.25 vs. 1.69±0.30, t=4.33, P<0.05). With the development of obesity, the hepatic gluconeogenesis was over-activated, indicating that the expression of Dancr may be associated with the activation of hepatic gluconeogenesis. Dancr expressions in tissues of heart, liver, spleen, lung, kidney, skeletal muscle, small intestine, stomach, white adipose tissue, brown adipose tissue and brain were significantly different (F=180.32, P<0.01). The expressions of Dancr in liver were significantly higher than those in other tissues except for spleen and lung (t=6.03–36.19, all P<0.01). Bioinformatic analysis found that Dancr was located on chromosome 5 (chr5:74 093 083-74 090 355) with the nucleic acid length of 1 060 bp including two exons. The results also revealed that Dancr had nine interactive miRNAs (mmu-let-7i-5p, mmu-miR-134-5p, mmu-miR-326-5p, mmu-miR-433-5p, mmu-miR-497-5p, mmu-miR-504-3p, mmu-miR-1906, mmu-miR-432, mmu-miR-5620-5p) and regulated 2 124 downstream target genes, including nine genes related to hepatic gluconeogenesis. Conclusion The expression of Dancr is influenced by physiological and pathological gluconeogenesis, and may be involved in the pathophysiologic processes of hepatic gluconeogenesis. Dancr bioinformatic analyses can provide data support for subsequent studies, further reveal the molecular mechanisms of gluconeogenesis. Key words: Long non-coding RNA; Dancr; Bioinformatics analysis; MicroRNAs; Hepatic gluconeogenesis