Methylation and HIF1 as regulators of miR-711 and its impact on stress-induced cell death

甲基化和 HIF1 作为 miR-711 的调节剂及其对应激诱导的细胞死亡的影响

• 批准号: RGPIN-2014-03908
• 负责人: Zheng, Xiufen
• 金额: $ 2.55万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=587486
• 关键词: Methylation; HIF1; regulators; miR; 711

In response to stress, cells adapt by altering their gene expression programs, and respond in a variety of ways ranging from the activation of survival pathways to the initiation of cell death, depending on the severity and duration of stress encountered. The mechanism of adaptation to stressful events remains unclear. Cardiomyocytes are cardiac muscle cells comprising cardiac muscle and a key player in forming heart function. We have demonstrated that hypoxia (low oxygen) and oxidative stress that are common stress induce cell death and organ dysfunction through activation of different signals. Recent studies have shown that small single-strand nucleotide ribosome acid (RNA) called as microRNA (miRNA) produced by a cell itself are changed upon exposure to stress. Our preliminary study also demonstrates that hypoxia stress significantly changes miR-711(one of miRNAs) expression in cardiomyocytes. By inhibiting various target molecules, miRNAs play crucial roles in various cellular processes and disease development. Due to their capacity to inhibite multiple target genes and their reversible regulation, miRNAs have emerged as a key controller of rapid cell responses to environmental changes and stress. However, how miR-711 is regulated and how miR-711 modulates cell death under stress is unclear. In this proposed study, we aim to investigate how microRNAs are regulated and their roles and function in response to low oxygen and oxidative stress through a series of cell culture experiments. The success of the study will provide new insight into understanding the mechanisms by which microRNAs function in stress responses. It will help understand how miRNAs are regulated and generated. It will also offer an excellent training environment for trainees.

在应对压力时，细胞通过改变其基因表达程序来适应，并以多种方式做出反应，从激活生存途径到启动细胞死亡，这取决于所遇到的压力的严重程度和持续时间。对应激事件的适应机制尚不清楚。心肌细胞是构成心肌的心肌细胞，是形成心脏功能的关键因素。我们已经证明，缺氧（低氧）和氧化应激是常见的应激诱导细胞死亡和器官功能障碍，通过激活不同的信号。最近的研究表明，由细胞自身产生的小单链核苷酸核糖体酸（RNA）称为microRNA（miRNA）在暴露于压力时发生变化。我们的初步研究还表明，缺氧应激显著改变了心肌细胞中miR-711（miRNAs之一）的表达。 通过抑制各种靶分子，miRNAs在各种细胞过程和疾病发展中起着至关重要的作用。由于它们能够激活多个靶基因及其可逆调节，miRNA已成为细胞对环境变化和应激的快速反应的关键控制器。然而，miR-711是如何调节的，以及miR-711如何调节应激下的细胞死亡尚不清楚。在这项拟议的研究中，我们的目的是通过一系列的细胞培养实验来研究microRNA是如何调节的，以及它们在低氧和氧化应激反应中的作用和功能。 这项研究的成功将为理解microRNA在应激反应中的作用机制提供新的见解。这将有助于了解miRNAs是如何调节和产生的。它还将为学员提供一个良好的培训环境。