The mechanisms of lncRNA Tug1 in islet dysfunction in a mouse model of intrauterine growth retardation

Abstract

Taurine upregulated gene 1 (Tug1) is a novel lncRNA that participates in growth, and the abnormal expression of Tug1 related to mouse islet cell dysfunction. A recent study revealed that intrauterine growth retardation (IUGR) related to the pathogenesis of diabetes. Here, we aimed to explore the role and mechanism of Tug1 in IUGRmediated islet dysfunction. We observed that newborn IUGR mice had lower body and pancreas weight and smaller islets than newborn control mice. After IUGR mice were given a normal diet, they showed catch-up growth and abnormal glucose tolerance; however, the pancreas/body weight ratio remained low. Blood glucose, serum insulin and related gene expression showed mild recovery after overexpression of Tug1 in IUGR mice. Furthermore, Tug1 was enriched in the nuclei of MIN6 cells. Using RIP and CHIP analyses we found that Tug1 could regulate Hes1 expression by binding to EZH2 to affect insulin synthesis in MIN6 cells. These findings indicate that lncRNA Tug1 could regulate the expression of Hes1 via EZH2-driven H3K27 methylation and affect insulin production.

lncRNA TUG1 regulates Smac/DIABLO expression by competitively inhibiting miR-29b and modulates the apoptosis of lens epithelial cells in age-related cataracts

“…As a novel lncRNA, TUG1 is involved in various biological processes. TUG1 has been widely studied in the field of oncology, and its differential expression in tumors can affect the proliferation and apoptosis of tumor cells and regulate tumor development [37] . Studies have shown that TUG1 can function as an oncogene or tumor suppressor gene.…”

Epigenetic Mechanisms Responsible for the Transgenerational Inheritance of Intrauterine Growth Restriction Phenotypes

“…However, at 12 months of age, they developed insulin resistance ( 93 ). On the other hand, in pancreatic islets of growth restricted mice whose mothers were fed a low-protein diet, the expression of Tug1 , a lncRNA that involves in diabetes and tumour development, were significantly lower at 1 day, 8 weeks, and 12 weeks post-partum, compared to the control ( 54 ). The aberrant glucose tolerance observed at 10 weeks old IUGR mice could be partially rescued by injection of 150 µg of Tug1 overexpression sequence, suggesting that Tug1 may play an important role in the mouse pancreatic development and function ( 54 ).…”

“…Animal studies that specifically focused on altered epigenetic mechanisms in the UPI-induced IUGR offspring have also been carried out in different organs and tissues [ Figure 2 ( 44 , 49 , 51 , 53 , 54 , 61 – 68 )]. Decreased expression, by 19% the control, of Dnmt3a , a gene that is responsible for de novo DNA methylation was found in kidney tissues of F1 IUGR rats at embryonic day 20 ( 53 ).…”

Long noncoding RNA‐dependent methylation of nonhistone proteins

“…In all the species identified, TUG1 has shown the capability to bind to EZH2. However, we noticed that both human and mouse TUG1 exploit the EZH2 activity to regulate the chromatin conformation (Huang et al, 2015;Katsushima et al, 2016;Y. Li, Dai, et al, 2020;Yu et al, 2019;E.…”