Sensor-seq: A genome-wide biological measure of microRNA activity.

描述（由申请人提供）：microRNA （miRNA）是最近发现的一类调节rna，有助于调节基因表达和控制细胞功能。已经发现了2000多种人类mirna。许多miRNA具有抑瘤或致癌功能，miRNA失调已被证明在肿瘤发生、转移甚至化疗耐药中发挥关键作用。尽管我们对miRNA生物学已经了解了很多，但随着新miRNA基因的发现，对相关miRNA调控网络的注释变得越来越具有挑战性。一个关键的限制是缺乏对miRNA行为进行全基因组分析的高通量生物学方法。在这个R33提案中，我们将开发和验证一种新的技术和方法，可用于：(1)以单细胞分辨率测量细胞内每个miRNA的活性；

DESCRIPTION (provided by applicant): microRNA (miRNA) are a recently uncovered class of regulatory RNAs which help to regulate gene expression, and control cell function. Over 2,000 human miRNAs have been discovered. Many miRNAs have tumor suppressor or oncogenic functions, and miRNA dysregulation has been shown to play a key role oncogenesis, metastasis, and even chemoresistance. Although much has been learned about miRNA biology, as the number of new miRNA genes have been discovered it has become increasingly challenging to annotate relevant miRNA regulatory networks. A critical limitation has been the lack of high-throughput, biological approaches for genome-wide analysis of miRNA behavior. In this R33 proposal, we will develop and validate a new technology and methodology that can be used to: (1) Measure the activity of each and every miRNA within a cell, at single cell resolution, and (2) Identify optimal synthetic miRNA binding sites that can be used to improve the targeting of suicide vectors and oncolytic viruses being developed for cancer therapies. Our technology will have major utility for expanding our understanding of cancer biology, for generating tools to study and even track specific cancer cell subsets, such as cancer stem cells, for screening for miRNA modulating drugs, and for developing novel therapies that better target tumor cells for destruction.