Cancer prevalence is still increasing. Despite numerous new treatments, mortality remains high, notably because of cancer cell resistance to drugs used in chemotherapy. We have previously shown that hypoxia protects several cancer cell lines against chemotherapy-induced apoptosis. Using one of these models (HepG2 cell line) and via a large screen approach, we identified several miRNAs which may be associated to hypoxia-induced chemoresistance. Three of them have been validated in vitro by functional studies: transfection with pre-miR or LNA-miR targeting each of them modulated drug-induced apoptosis. The aim of the project is to identify mRNA targets of these miRNAs that are responsible for apoptosis regulation and that can be used as chemoresistance biomarkers. This will be performed through AGO2 immunoprecipitation and high throughput sequencing (RIP-Seq : RNA ImmunoPrecipitation Sequencing). A proteomic approach will be also performed to identify mRNA targets. Computational correlation studies and studies on human tumor biopsies will be also performed to determine if a correlation exists between the expression of miRNAs and/or the target mRNA and response to treatment.
|Effective start/end date||1/10/13 → 30/09/15|