Direct Regulation of an Oncogenic Micro-RNA Cluster by E2F Transcription Factors

Micro-RNAs (miRNAs) are a class of non-coding RNAs that post-transcriptionally regulate gene expression via the RNA interference pathway. In addition to roles in normal development, miRNAs have recently been implicated in a range of human diseases, including cancer. We recently demonstrated that a p...

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Bibliographic Details
Published in:The Journal of biological chemistry 2007-01, Vol.282 (4), p.2130-2134
Main Authors: Woods, Keith, Thomson, J. Michael, Hammond, Scott M.
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Base Sequence
E2F Transcription Factors - genetics
E2F Transcription Factors - metabolism
Gene Expression Regulation
Humans
Mice
MicroRNAs - genetics
MicroRNAs - metabolism
Models, Genetic
Molecular Sequence Data
Promoter Regions, Genetic
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Summary:Micro-RNAs (miRNAs) are a class of non-coding RNAs that post-transcriptionally regulate gene expression via the RNA interference pathway. In addition to roles in normal development, miRNAs have recently been implicated in a range of human diseases, including cancer. We recently demonstrated that a polycistronic cluster of miRNAs, miR-17–92, is oncogenic in a mouse model for Burkitt's lymphoma. This is due, in part, to a reduced apoptotic program. In an effort to understand the regulation of miR-17–92, we have studied the promoter structure of this miRNA cluster. The primary transcript initiates from a consensus initiator sequence downstream of a nonconsensus TATA box. The core promoter region contains two functional E2F transcription factor binding sites. Chromatin immunoprecipitation demonstrates that E2F3 is the primary E2F family member that occupies the promoter. These data place miR-17–92 in a regulatory loop between E2F3 and the miR-17 target E2F1. We propose a model whereby miR-17–92 promotes cell proliferation by shifting the E2F transcriptional balance away from the pro-apoptotic E2F1 and toward the proliferative E2F3 transcriptional network.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.C600252200