Studies of genetic alterations that contribute to tumor development have focused almost exclusively on protein coding genes. It is now clear that the genome generates a variety of non-coding RNAs that have widespread and important roles in gene regulation. The microRNAs are an abundant class of small RNAs that modulate mRNA expression and stability through the RNAi pathway. A number of these genes have been implicated as oncogenes and tumor suppressors. In this Project, we propose to investigate the biological function on a bona fide microRNA oncogene, mir-17-92. The ultimate goal of Project 5 is to understand the precise mechanism through which mir-17-92 contributes to tumor development. This will be accomplished through structure-function studies of the microRNA polycistron and through the identification of the mRNA targets of its key oncogenic components. Additionally, we will probe the normal biological function of this oncogene through the generation and characterization of both gain-of-function and loss-of- function mutants. Finally, we will explore more broadly the role of the microRNA machinery in tumor development through genetic manipulation of the microRNA biogenesis machinery and through a search for microRNAs that show expression changes in breast carcinoma, hepatocellular carcinoma and B-cell lymphoma.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA013106-39
Application #
8018466
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2010-01-01
Budget End
2010-12-31
Support Year
39
Fiscal Year
2010
Total Cost
$684,342
Indirect Cost
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724
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