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Identifying novel regulatory mechanisms of miRNA functions

Objective

microRNAs (miRNAs) are master regulators of gene expression capable of defining and altering cell identity. Because of their potency, small size, simple mode of action (target recognition through a Watson-Crick type of base pairing) and the possibility to inhibit them in vivo, miRNAs are valuable therapeutic targets. Recently, we have used novel functional-genetic screening approaches and identified the miR-372, 373 and 520, as well as the miR-221&222 family as cancerous miRNAs. These miRNAs are oncogenes, as they are deregulated in specific types of cancers, target tumor suppressors and their inhibition reverts cancerous phenotypes. However, at present almost nothing is known about the mechanisms governing the expression and function of these, as well as many other, oncogenic miRNAs. Here, I propose experiments to identify and characterize factors affecting the activity of oncogenic miRNAs using an array of molecular and genetic tools. Our preliminary results indicate the existence of novel regulators and mechanisms of miRNA activity. We therefore believe that the information collected here not only will lead to a better understanding of miRNA functions, but will also identify novel modes of manipulating miRNA activity in human disease.

Call for proposal

ERC-2007-StG
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Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
Address
Plesmanlaan 121
1066 CX Amsterdam
Netherlands
Activity type
Research Organisations
EU contribution
€ 1 349 760
Principal investigator
Reuven Agami (Dr.)
Administrative Contact
Henri Van Luenen (Dr.)

Beneficiaries (1)

STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
Netherlands
EU contribution
€ 1 349 760
Address
Plesmanlaan 121
1066 CX Amsterdam
Activity type
Research Organisations
Principal investigator
Reuven Agami (Dr.)
Administrative Contact
Henri Van Luenen (Dr.)