RNA as a Hormone: Systemic Signaling in Mammals via Circulating, Cell-Free Small

RNA 作为激素：哺乳动物中通过循环、无细胞小分子的系统信号传导

• 批准号: 7937011
• 负责人: MUNEESH TEWARI
• 金额: $ 69.3万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7937011
• 关键词: Animals; Blood; Blood Circulation; Cells; Diagnosis; Disease; Distant; Endocrine system; Health; Hematopoietic Neoplasms; Hormones; Human; Human body; Lead; Malignant Neoplasms; Mammals; Methods; MicroRNAs; Motivation; Organ; Organism; Physiology; Plants; RNA; Series; Signal Transduction; Site; Tissues; Travel; base; cancer cell; fly; human disease; mouse model; public health relevance

DESCRIPTION (provided by applicant): This proposal seeks to establish the new scientific paradigm that RNA molecules can function as hormones, traveling via the bloodstream to target organs where they are taken up and influence the activity of specific recipient cells. The conventional paradigm of the endocrine system does not include RNA molecules as a class of hormones. The motivation for trying to establish this paradigm comes from a series of facts: (i) RNA molecules have been shown to function as hormones in plants, (ii) in some animal species (e.g., worms and flies) RNA has been shown to spread throughout the organism and carry information from one site to another, and (iii) we and others have found that at least one class of RNAs, known as microRNAs, are abundantly present in the blood of healthy humans and specific microRNAs accumulate in disease states such as cancer. To establish this new paradigm, we will focus on microRNAs secreted into the blood by cancer cells and use mouse models to determine whether the microRNAs are taken up by and influence distant organs and tissues. In addition, we will purify microRNAs in their natural state from blood and determine whether if re-injected into the bloodstream they can travel to specific target sites and have a hormone-like action. Establishing this new paradigm would have a major impact not only on basic understanding of human physiology but could also open up new ways of diagnosing and treating disease based on RNA hormones in the blood. PUBLIC HEALTH RELEVANCE: This proposal is highly relevant to human health because it seeks to identify a new type of hormone molecule that we hypothesize carries signals throughout the human body. Establishing that RNA molecules in the blood can act as hormones could lead to better methods of diagnosing and treating a variety of human diseases.

描述（由申请人提供）：该提案旨在建立新的科学范式，即RNA分子可以作为激素发挥作用，通过血流到达靶器官，在那里它们被吸收并影响特定受体细胞的活性。内分泌系统的常规范例不包括RNA分子作为一类激素。试图建立这种范式的动机来自一系列事实：（i）RNA分子已被证明在植物中起激素的作用，（ii）在一些动物物种中（例如，蠕虫和苍蝇）RNA已被证明可以在整个生物体中传播，并将信息从一个位置传递到另一个位置，（iii）我们和其他人发现至少有一类RNA，称为microRNA，大量存在于健康人的血液中，并且特定的microRNA在疾病状态（如癌症）中积累。为了建立这种新的范式，我们将专注于癌细胞分泌到血液中的microRNA，并使用小鼠模型来确定microRNA是否被远处的器官和组织吸收并影响它们。此外，我们将从血液中纯化处于自然状态的microRNA，并确定如果重新注射到血液中，它们是否可以到达特定的靶位点并具有类似于血液的作用。建立这种新的范式不仅会对人类生理学的基本理解产生重大影响，而且还可以开辟基于血液中RNA激素诊断和治疗疾病的新方法。 公共卫生相关性：这项提议与人类健康高度相关，因为它试图确定一种新型的激素分子，我们假设这种分子在整个人体内携带信号。确定血液中的RNA分子可以作为激素发挥作用，可能会导致更好的诊断和治疗各种人类疾病的方法。