LncRNA LEGLTBC Functions as a ceRNA to Antagonize the Effects of miR-34a on the Downregulation of SIRT1 in Glucolipotoxicity-Induced INS-1 Beta Cell Oxidative Stress and Apoptosis
LncRNA LEGLTBC Functions as a ceRNA to Antagonize the Effects of miR-34a on the Downregulation of SIRT1 in Glucolipotoxicity-Induced INS-1 Beta Cell Oxidative Stress and Apoptosis
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LncRNA LEGLTBC 作为 ceRNA 发挥作用，在糖脂毒性诱导的 INS-1 Beta 细胞氧化应激和细胞凋亡中拮抗 miR-34a 对 SIRT1 下调的影响。
DOI：
10.1155/2019/4010764
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发表时间：
2019-10-14
影响因子：
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通讯作者：
Lv, Kun
中科院分区：
文献类型：
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作者：
Kong, Xiang;Liu, Chong-xiao;Lv, Kun
2型糖尿病是一种慢性代谢紊乱，其特征在于血糖升高和/或血清游离脂肪酸升高。慢性高脂血症导致胰腺β细胞功能障碍，在高血糖症存在下加重（糖脂毒性）。长链非编码RNA（lncRNA）被认为在1型糖尿病的发生发展中起关键作用。然而，它们在糖脂毒性诱导的β细胞功能障碍中的作用尚未完全了解。在本研究中，我们确定了差异表达的lncRNA在INS-1细胞暴露于高糖和棕榈酸（HG/PA）。在失调的lncRNA中，NONRATT003679.2（在糖脂毒性处理的β细胞（LEGLTBC）中低表达）参与糖脂毒性诱发的大鼠胰岛β细胞损伤。LEGLTBC在INS-1细胞中充当miR-34 a的分子海绵。此外，SIRT 1被鉴定为miR-34 a的靶点，并且LEGLTBC通过海绵状吸收miR-34 a来促进SIRT 1表达。LEGLTBC的上调通过促进SIRT 1介导的ROS积累和凋亡的抑制来减轻HG/PA诱导的INS-1细胞损伤。这是第一项全面鉴定HG/PA处理的INS-1 β细胞的lncRNA表达谱的研究，并证明LEGLTBC作为竞争性内源性RNA发挥作用，并调节经历糖脂毒性的INS-1细胞中miR-34 a/SIRT 1介导的氧化应激和凋亡。
Type 2 diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose and/or high serum free fatty acids. Chronic hyperlipidemia causes the dysfunction of pancreatic beta cells, which is aggravated in the presence of hyperglycemia (glucolipotoxicity). Long noncoding RNAs (lncRNAs) have been suggested to play key roles in type 1 diabetes mellitus development. However, their roles in glucolipotoxicity-induced beta cell dysfunction are not fully understood. In the present study, we identified the differentially expressed lncRNAs in INS-1 cells exposed to high glucose and palmitate (HG/PA). Among the dysregulated lncRNAs, NONRATT003679.2 (low expression in glucolipotoxicity-treated beta cells (LEGLTBC)) was involved in glucolipotoxicity-evoked rat islet beta cell damage. LEGLTBC functioned as a molecular sponge of miR-34a in INS-1 cells. Additionally, SIRT1 was identified as a target of miR-34a and LEGLTBC promoted SIRT1 expression by sponging miR-34a. The upregulation of LEGLTBC attenuated HG/PA-induced INS-1 cell injury through the promotion of SIRT1-mediated suppression of ROS accumulation and apoptosis. This is the first study to comprehensively identify the lncRNA expression profiling of HG/PA-treated INS-1 beta cells and to demonstrate that LEGLTBC functions as a competing endogenous RNA and regulates miR-34a/SIRT1-mediated oxidative stress and apoptosis in INS-1 cells undergoing glucolipotoxicity.