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: 10005921
• 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/10005921
• 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.

项目概要/摘要 该提案“长链非编码RNA在正常细胞和癌细胞中的调节作用”正在提交 响应 PAR-17-049，“研究专家（实验室科学家）奖 (R50)”，来自 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 计划，但不担任独立调查员。 该提案基于 Daniel G. Tenen 博士于 2017 年获得的杰出研究者奖 (R35) 对 PAR-14-267 的回应，标题为“急性髓系白血病中 RNA 的调节机制”。 近年来，研究人员发现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) 提供了额外且相对 许多生物过程的未探索的控制层。 R35提案的总体目标是 以急性髓系白血病 (AML) 作为研究对象，研究癌症中 RNA 控制的尚未探索的方面 研究模型。 研究科学家的贡献旨在理解癌症的背景 通过解决以下领域，研究 RNA 所发挥的机制作用：（1） 非编码 RNA，限制肿瘤抑制基因 PU.1 的表达，特别是在特定的 白血病的亚型； (2) ncRNA 调节 DNA 等表观遗传变化的能力 甲基化，最终目标是开发基因选择性去甲基化工具以及识别 其他受 ncRNA 调控的表观遗传标记。这些研究将在每种情况下寻求调查 ncRNA 在癌症中的作用，以及更具体的治疗方式的潜在开发。 此外，对于 Tenen 博士的 R35 提案中列出的目标，我建议在以下范围内扩展研究： 以下研究领域： (i) 了解 lncRNA 在维持基因组 DNA 稳定性方面的作用； (二) 了解 lncRNA 在转录活性染色质形成中的作用； (iii) 身份证明 参与维持急性髓性白血病基因组DNA稳定性的lncRNA。 这些新方向的实现将是 Tenen 博士提出的想法的逻辑延续。 应用并可能为未来的转化工作铺平道路。