Skip to main content

Targeting microRNAs for ColoRectal Cancer Therapy

Objective

MicroRNAs are small non-coding RNAs involved in cell homeostasis and carcinogenesis. MicroRNA deregulation is associated with colorectal cancer (CRC) progression. My study proposes to identify genetic and epigenetic events leading to microRNAs deregulation and use them as targets for drug development. My research proposal will address two important questions. First it will assess the contribution of genetic and epigenetic events in controlling microRNA genes and cancer phenotype. Second it will define synthetic lethal interaction between microRNA genes aberration and kinase genes in order to define novel target for therapy.
Mutations and promoter methylation of microRNA genes and microRNA processing genes will be analyzed by massive parallel sequencing in a first cohort of CRC. Mathematical and in vitro analysis will be performed to test whether a mutation is a driver or passenger one. The frequency of driver mutations and promoter methylation will be confirmed in a large case-control study encompassing 2500 CRC patients. Mutational and methylation status will be matched with clinical-pathological features in order to detect correlations with clinical outcome. In order to translate my findings into drug development, genetic aberration in microRNA genes will be reproduced in CRC cell lines. Isogenic cell lines harboring the wild type or the mutant allele will be tested for cell viability in a parallel RNAi screening using siRNA libraries targeting kinase. Protein kinases are important mediators of microRNA function. More importantly, catalytic inhibitors of kinase can be easily developed making them attractive targets for synthetic lethality screening and drug development.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/rna
  • /medical and health sciences/basic medicine/physiology/homeostasis
  • /natural sciences/biological sciences/genetics and heredity/mutation
  • /medical and health sciences/clinical medicine/oncology/cancer
  • /medical and health sciences/clinical medicine/oncology/cancer/colorectal cancer

Call for proposal

FP7-PEOPLE-2012-CIG
See other projects for this call

Funding Scheme

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

THE INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL
Address
Old Brompton Road 123
SW7 3RP London
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 9 341,39
Administrative Contact
Angus Bell (Dr.)

Participants (1)

UNIVERSITY OF GLASGOW

Participation ended

United Kingdom
EU contribution
€ 90 658,61
Address
University Avenue
G12 8QQ Glasgow
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Derek Motherwell (Mr.)