Regulatory role of long noncoding RNAs in normal and cancer cells

长非编码RNA在正常细胞和癌细胞中的调节作用

• 批准号: 9768983
• 负责人: Alexander K Ebralidze
• 金额: $ 26.13万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-19 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9768983
• 关键词: Acute Myelocytic Leukemia; Address; Antisense RNA; Area; Award; Biological Process; Biology; Cancer Research Project; Chromatin; Complex; DNA; DNA Maintenance; DNA Methylation; Development; Disease; Environment; Epigenetic Process; Explosion; Future; Genes; Genetic Transcription; Genome; Genome Stability; Genomic DNA; Goals; Laboratories; Malignant Neoplasms; Methods; Methylation; Modality; National Cancer Institute; Normal Cell; Organism; Play; Process; RNA; Regulation; Research; Research Personnel; Role; Scientist; Specialist; Study models; Therapeutic; Tumor Suppressor Genes; Untranslated RNA; base; cancer cell; career; design; leukemia; novel; response; tool

Project Summary/Abstract This proposal, " Regulatory role of long noncoding RNAs in normal and cancer cells”, is being submitted in response to PAR-17-049, "Research Specialist (laboratory-based Scientists) Award (R50)", from the National Cancer Institute. The Award is designed to encourage the development of stable research career opportunities for exceptional scientists who want to pursue research within the context of an existing cancer research program, but not serve as independent investigators. This proposal is built on the Outstanding Investigator Award (R35) received by Dr. Daniel G. Tenen in response to PAR-14-267 and entitled "Mechanisms of regulation by RNA in acute myeloid leukemia”. In recent years researchers have revealed that a large portion of the genome of complex organisms are transcribed but not translated. These noncoding RNAs (ncRNAs) provide an additional and relatively unexplored layer of control to many biological processes. The overall goal of the R35 proposal is to investigate underexplored aspects of RNA control in cancer, using acute myeloid leukemia (AML) as a model of study. The contribution of the Research Scientist will aim at understanding, in the context of a cancer environment, the mechanistic role played by RNAs, by addressing the following areas: (1) the study of a noncoding RNA which limits expression of the tumor suppressor gene PU.1, particularly in a specific subsets of leukemias; and (2) the ability of ncRNA to regulate epigenetic changes such as DNA methylation, with the ultimate goal of developing gene-selective demethylating tools as well as identifying other epigenetic marks regulated by ncRNAs. These studies will, in every instance, seek to investigate the role of ncRNAs in cancer, as well as potential development of more specific therapeutic modalities. In addition, to the goals listed in the Dr. Tenen’s R35 proposal, I propose to extend the studies within the following research areas: (i) Understanding the role of lncRNAs in maintaining stability of genomic DNA; (ii) Understanding the role of lncRNAs in formation of transcriptionally active chromatin; and (iii) Identification of lncRNAs involved in maintaining stability of the genomic DNA in acute myeloid leukemia. Fulfilment of these new directions will be a logical continuation of the ideas proposed in Dr. Tenen’s application and might pave the way for the future translational efforts.

项目摘要/摘要 该提案“正在正常和癌细胞中长期非编码RNA的调节作用”正在提交 为了回应17-049年的“研究专家（基于实验室的科学家）奖（R50）”， 国家癌症研究所。 该奖项旨在鼓励发展稳定的研究职业机会 想要在现有癌症研究的背景下进行研究的杰出科学家 程序，但不作为独立调查员。 该提案建立在丹尼尔·G·塔宁博士的杰出调查员奖（R35）上 对PAR-14-267的反应和题为“ RNA在急性髓样白血病中调节的机制”。 近年来，研究人员透露，复杂生物体的大部分基因组是 转录但未翻译。这些非编码RNA（NCRNA）提供了额外的相对和相对 未探索的控制层到许多生物过程。 R35提案的总体目标是 使用急性髓样白血病（AML）作为一种 研究模型。 研究科学家的贡献将在癌症的背景下理解 环境是RNA扮演的机械作用，通过解决以下领域：（1）研究 非编码RNA限制了肿瘤抑制基因PU.1的表达，特别是在特定中 白血病的子集； （2）NCRNA调节表观遗传变化（例如DNA）的能力 甲基化，其最终目标是开发基因选择性脱甲基化工具并识别 其他由NCRNA调节的表观遗传标记。这些研究将在任何情况下都试图调查 NCRNA在癌症中的作用，以及更具体的治疗方式的潜在发展。 此外，对于Tenen博士的R35提案中列出的目标，我提议将研究扩展 以下研究领域：（i）了解LNCRNA在保持基因组DNA稳定性方面的作用； （ii） 了解LNCRNA在转录活性染色质形成中的作用； （iii）识别 LNCRNA参与急性髓样白血病中基因组DNA的稳定性。 实现这些新方向将是Tenen博士提出的想法的逻辑延续 应用，可能为未来的翻译工作铺平道路。