MicroRNAs, cardiac function and cardiomyopathy

MicroRNA、心脏功能和心肌病

• 批准号: 10559334
• 负责人: Da-Zhi Wang
• 金额: $ 1.22万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-21 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10559334
• 关键词: MicroRNAs; cardiac; function; cardiomyopathy

Contact PD/PI: Wang, Da-Zhi Cardiovascular disease is the leading cause of death in United States. However, the molecular events that control heart development and cardiac function are not fully understood. MicroRNAs (miRNAs) are a class of small regulatory RNA molecules found in most organisms. Emerging evidence has established that miRNAs play important regulatory roles, mainly by degrading target messenger RNAs (mRNAs) and/or inhibiting translation of protein-coding mRNAs in a variety of biological processes, including cell proliferation, differentiation and survival. miRNAs are also implicated in many human diseases, including cardiovascular disease. The discovery of miRNAs and their potential biological functions in regulating gene expression opened a completely new field to investigate how miRNAs participate in “classical” gene expression pathways. To date, more than 2,000 miRNAs have been identified in humans; however, the molecular mechanisms and the in vivo functions of most miRNAs remain unknown. The overall goal of this study is to define the biological function and the molecular mechanisms of miRNAs in the heart. Our central hypothesis is that miRNAs are components of the molecular circuitry that controls cardiac gene expression and function. More specifically, we will test our hypothesis that the Trbp-miR-208a pathway regulates cardiac function is a context-dependent manner. We present three integrative aims to test our hypothesis: Aim #1. What is the function of Trbp in the heart under pathophysiological stresses? Aim #2. How is the specificity of Trbp function in the miRNA pathway defined in the heart? Aim #3. What is the role of miR-208a in the heart and how does it work? Our studies will provide important insights into the molecular mechanisms by which miRNAs control mammalian heart development, function and cardiac gene expression. The molecular strategies we uncover in these studies will help define the ontogenesis of heart failure with potential broader implications for understanding the pathophysiology of cardiac disease in humans. Project Summary/Abstract Page 6

联系PD/PI：王大志 心血管疾病是美国的主要死亡原因。然而，分子 控制心脏发育和心脏功能的事件尚不完全清楚。 MicroRNAs(MiRNAs)是一类存在于大多数生物体中的小调节RNA分子。 新出现的证据表明，miRNAs发挥着重要的调节作用，主要是通过 降解靶信使RNA和/或抑制蛋白质编码的翻译 MRNAs参与多种生物过程，包括细胞增殖、分化和 生死存亡。MiRNAs还与许多人类疾病有关，包括心血管疾病 疾病。MiRNAs的发现及其在基因调控中的潜在生物学功能 表达开启了一个全新的领域来研究miRNAs是如何参与“经典”的 基因表达途径。到目前为止，已经在人类身上发现了2000多个miRNAs； 然而，大多数miRNAs的分子机制和体内功能仍然存在。 未知。 本研究的总体目标是确定其生物学功能和分子机制。 心脏中的miRNAs。我们的中心假设是miRNAs是 控制心脏基因表达和功能的分子回路。更具体地说，我们 将检验我们的假设，即TRBP-miR-208A途径调节心脏功能是一个 依赖于上下文的方式。我们提出了三个综合目标来检验我们的假设： 目的#1.在病理生理应激状态下，TRBP在心脏中的作用是什么？ 目的#2.TRBP在miRNA途径中的功能是如何定义的 心? 目标3.miR-208A在心脏中的作用是什么？它是如何发挥作用的？ 我们的研究将对miRNAs的分子机制提供重要的见解 控制哺乳动物心脏发育、功能和心脏基因表达。分子 我们在这些研究中发现的策略将有助于定义心力衰竭的个体发生 对了解心脏疾病病理生理学的潜在的更广泛的影响 人类。 项目摘要/摘要第6页

项目成果

Adeno-associated virus-mediated delivery of anti-miR-199a tough decoys attenuates cardiac hypertrophy by targeting PGC-1alpha.

• DOI: 10.1016/j.omtn.2020.11.007
• 发表时间: 2021-03-05
• 期刊: Molecular therapy. Nucleic acids
• 作者: Yan H;Wang H;Zhu X;Huang J;Li Y;Zhou K;Hua Y;Yan F;Wang DZ;Luo Y
• 通讯作者: Luo Y

Deletion of miRNA-22 Induces Cardiac Hypertrophy in Females but Attenuates Obesogenic Diet-Mediated Metabolic Disorders.

• DOI: 10.33594/000000309
• 发表时间: 2020-12-01
• 期刊: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
• 作者: de Oliveira Silva, Tabatha;Lino, Caroline A;Diniz, Gabriela P
• 通讯作者: Diniz, Gabriela P

Decreased miR-497-5p Suppresses IL-6 Induced Atrophy in Muscle Cells.

• DOI: 10.3390/cells10123527
• 发表时间: 2021-12-14
• 期刊: Cells
• 影响因子: 6
• 作者: Freire PP;Cury SS;Lopes LO;Fernandez GJ;Liu J;de Moraes LN;de Oliveira G;Oliveira JS;de Moraes D;Cabral-Marques O;Dal-Pai-Silva M;Hu X;Wang DZ;Carvalho RF
• 通讯作者: Carvalho RF