Noncoding RNAs as prognostic markers and therapeutic targets in breast cancer

非编码RNA作为乳腺癌的预后标志物和治疗靶点

• 批准号: nhmrc : 456080
• 负责人: Prof John Mattick
• 金额: $ 36.69万
• 依托单位: The University of Queensland
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/noncoding-rnas-prognostic-breast-cancer/81046
• 关键词: Noncoding; RNAs; prognostic; markers; therapeutic

Normal human development involves a symphony of genetic changes that control the growth and differentiation of different types of cells during embryogenesis. For many years it has been assumed that most genetic information is transacted by proteins, and that the remaining 98% of the human genome that does not encode proteins was (apart from a limited amount of associated regulatory elements) largely non-functional evolutionary junk. However, this may not be the case. Recent results from our laboratory and others have shown that most of our genome and that of other mammals is actually expressed as noncoding RNA, which appears to be developmentally regulated. These RNAs (of which there appear to be tens of thousands, well outnumbering the protein-coding mRNAs) have been referred to as the hidden layer or dark matter of our genome, as they have barely been studied, but appear to play a central role in both normal and abnormal development in humans. There is now increasing evidence that many noncoding RNAs, including small regulatory RNAs called microRNAs, are perturbed in cancer and that these perturbations may be directly involved in, and be an accurate indicator of, cancer state and the direction of cancer progression. If this is true we need to understand the expression and functions of these RNAs in order to develop better diagnostics and perhaps powerful new therapeutics for cancer, based on RNA technology and generic delivery systems. This project will explore the patterns of noncoding RNA expression in normal breast development and in breast cancer, to identify those RNAs that direct or accompany the differentiation of these tissues, and to test the effects of interfering with their expression on these processes. These foundation studies lie at the leading edge of a new understanding of human genetics and cancer, and will provide a platform for future applications in medicine that utilize this information and understanding.

正常的人类发育涉及一系列遗传变化，这些变化控制着胚胎发育过程中不同类型细胞的生长和分化。多年来，人们一直认为大多数遗传信息是由蛋白质处理的，剩下的98%的人类基因组不编码蛋白质（除了有限数量的相关调控元件）基本上是无功能的进化垃圾。然而，情况可能并非如此。我们实验室和其他实验室的最新结果表明，我们和其他哺乳动物的大部分基因组实际上是以非编码RNA的形式表达的，这似乎是受发育调控的。这些RNA（似乎有数万种，远远超过了蛋白质编码mRNA）被称为我们基因组的隐藏层或暗物质，因为它们几乎没有被研究过，但似乎在人类的正常和异常发育中发挥着核心作用。现在有越来越多的证据表明，许多非编码RNA，包括称为microRNA的小调控RNA，在癌症中受到干扰，这些干扰可能直接参与癌症状态和癌症进展方向，并且是癌症状态和癌症进展方向的准确指标。如果这是真的，我们需要了解这些RNA的表达和功能，以便开发更好的诊断方法，并基于RNA技术和通用递送系统开发强大的癌症新疗法。该项目将探索非编码RNA在正常乳腺发育和乳腺癌中的表达模式，以识别指导或伴随这些组织分化的RNA，并测试干扰其表达对这些过程的影响。这些基础研究处于对人类遗传学和癌症的新理解的前沿，并将为利用这些信息和理解的未来医学应用提供平台。