| dc.description.abstract | The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long noncoding RNA and its overexpression is associated with poor prognosis of many types of cancers and its silencing has been reported to reverse the course of carcinogenesis in vitro and in vivo in laboratory animals. The MALAT1 is an evolutionarily conserved lncRNA with high level of expression in various tissues and cell types due to its unique stabilizing triple helix structure. Its genome-wide involvement in RNA splicing and transcriptional regulation suggests that it has of functionality in transcriptional regulation. However, its physiological functions are somewhat enigmatic as the MALALT1 null mice show no overt phenotype under normal laboratory conditions. Consistent with its pervasive involvement in gene regulation, results from recent studies indicate that MALAT1 has pleiotropic role in regulating physiological and pathophysiological functions. In this study, we revealed a salient feature of MALAT1 is its novel function in regulating oxidative stress and immune/inflammatory responses which are important etiological factors for many diseases. In transcriptome analysis of MALAT1 null mice we found significant upregulation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) regulated antioxidant genes with significant reduction in reactive oxygen species (ROS). MALAT1 null mice exhibited sensitized insulin-signaling response and alleviated lipopolysaccharide-induced innate immune response.
Furthermore, we established a mouse T2DM model, ob/ob model and investigated the role of MALAT1 in regulating the insulin signaling pathway and obesity. Consistent with our previous results, MALAT1 ablation alleviates the hyperglycemia, hyperinsulinemia, and insulin resistance in the obesity-induced T2DM in ob/ob mice, with significantly decreased fat deposition in liver and visceral adipose tissue. In summary, we demonstrate that MALAT1 plays an important role in regulating oxidative stress-mediated diseases and has the potential as a therapeutic target for the treatment of diseases caused by excessive exposure to ROS. | |
