Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
Department of Thoracic Surgery, Yixing Tumor Hospital, 45 East Dongshan Road, Yixing, Jiangsu Province, PR China.
Biomed Pharmacother. 2019 Oct;118:109256. doi: 10.1016/j.biopha.2019.109256. Epub 2019 Jul 27.
α-Mangostin play crucial role in several cellular progress, including hyperglycemia-induced inhibition of cell growth and promotion of cell apoptosis. Increasing evidence displayed the important roles of lncRNAs and their potential as novel targets for drug development in human disease. However, there is rare study to comprehensively and systematically explore the role and underlying mechanism of lncRNAs in human umbilical vein endothelial cells (HUVECs) under hyperglycemia with or without α-Mangostin. In this study, we firstly found that α-Mangostin reduced the high glucose-induced inhibition of cell proliferation and migration potential of HUVECs. Then, we performed RNA-seq to dissect the expression profiles of lncRNAs in HUVECs treated with high glucose or high glucose supplemented with α-Mangostin. The results showed that the expression of H19 and HE4 was down-regulated by high glucose and further, α-Mangostin restored the high glucose-induced inhibition of H19 and HE4 expression. Further examination demonstrated that the modulation of the H19 and HE4 expression affected the function of α-Mangostin in hyperglycemia. In addition, H19 regulated HE4 expression via the modulation of the miR-140 expression. Finally, we showed that H19 exerted its function via the modulation of H19/miR-140/HE4 in hyperglycemia with α-Mangostin. In summary, this study is the first to comprehensively identify the lncRNAs/mRNAs network in hyperglycemia with or without α-Mangostin, highlighting a novel regulatory pathway in hyperglycemia with or without α-Mangostin and indicating the potential therapeutic role of α-Mangostin in diabetes mellitus.
α-倒捻子素在几种细胞进程中发挥关键作用，包括高血糖诱导的细胞生长抑制和促进细胞凋亡。越来越多的证据表明，lncRNAs 及其作为人类疾病药物开发新靶点的潜力非常重要。然而，很少有研究全面系统地探讨 lncRNAs 在高糖环境下或有或无 α-倒捻子素存在时对人脐静脉内皮细胞（HUVECs）的作用及其潜在机制。在本研究中，我们首先发现 α-倒捻子素降低了高糖诱导的 HUVECs 增殖和迁移潜能的抑制作用。然后，我们进行了 RNA-seq 以剖析 HUVECs 在用高糖或高糖补充 α-倒捻子素处理后的 lncRNAs 表达谱。结果表明，H19 和 HE4 的表达在高糖条件下被下调，而 α-倒捻子素进一步恢复了高糖诱导的 H19 和 HE4 表达抑制。进一步研究表明，H19 和 HE4 表达的调节影响了 α-倒捻子素在高糖环境下的功能。此外，H19 通过调节 miR-140 的表达来调节 HE4 的表达。最后，我们表明 H19 通过调节 H19/miR-140/HE4 在高糖与 α-倒捻子素共同作用下发挥其功能。总之，本研究首次全面鉴定了高糖环境下或有或无 α-倒捻子素存在时的 lncRNAs/mRNAs 网络，突出了高糖环境下或有或无 α-倒捻子素存在时的新调控途径，并表明了 α-倒捻子素在糖尿病治疗中的潜在作用。
