Computational Phenomics and Thorough Biological Characterization Uncovers a Novel Tumor Suppressor

Date

April 15, 2010, 6:00 pm – 7:00 pm

Location

KCBD, Room 1103
University of Chicago

Description

IGSB Fellows Seminar Series

Yves Lussier, M.D.
Associate Professor, Department of Medicine
Section of Genetic Medicine
The University of Chicago

“Computational Phenomics and Thorough Biological Characterization Uncovers
a Novel Tumor Suppressor microRNA and its Regulatory Network”

Thursday, April 15, 2010
4:00 p.m.

Knapp Center for Biomedical Discovery, Room 1103
900 E. 57th Street

Abstract:
MicroRNAs are important regulators of oncogenesis. Yet, genome-scale key regulatory networks and biological systems perturbed by altered microRNA functions in cancer remain to be identified since previous studies biologically confirmed only a few genes as microRNA targets. Here, we demonstrate for the first time how a large amount of phenotypic knowledge of inheritable cancer traits can be utilized jointly with microRNA-target predictions, based on sequence alignment, and with gene expression analysis to bioinformatically predict deregulated microRNAs, their targets, and their combined functions at multiple scales of biology. Our approach further uncovers previously unknown connections between microRNAs, gene network topology, and gene expression dynamics. We predict, in silico, the presence, functions, and gene targets of miR-204, a new tumor suppressor microRNA, in a head and neck cancer-associated genomic region where a candidate gene has not been identified. We then confirm their validity with thorough biological characterization in vitro and show reduction of lung metastasis in vivo. This is the first time that a large predicted microRNA-regulated network achieves full biological validation.


Liza Herendeen

Administrative Assistant

Institute for Genomics & Systems Biology

The University of Chicago

900 East 57th Street, KCBD 10100

Chicago, IL 60637

(773) 834-3913

Fax: (773) 834-2877

lherend1@bsd.uchicago.edu

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