Project:

"mRNA targeting regulation in androgen-independent prostate cancer pathogenesis (bioinformatics approach)

Prostate development and early-stage prostate cancers depend on androgens for growth and survival. Prostate cancers that are not cured by therapies based on androgen depletion, radiation, cryotherapy, chemotherapy and/or surgery invariably progress from initial androgen dependence to androgen independence. This group of prostate cancer patients eventually fail androgen ablation therapy and die of recurrent androgen-independent prostate cancer. Understanding the molecular factors that lead to this conversion will pave the way to effective therapies for these untreatable cancers.

Over the past few years, many microRNAs (miRNAs) have been implicated in various human cancers, including prostate cancer. Although, few miRNAs have been described to be either up- or downregulated in tumors, a global impairment of miRNA expression or mode of action has been observed in all cancers, indicating that mechanisms modulating miRNA pathway would favor tumorogenesis. Based on the observations described above, we hypothesize that the change of miRNA targeting programme plays a pivotal role in prostate cancer onset and progression to androgen independent state, which can be also used for the stratification of patients. Therefore, we propose to use Cross-Linking ImmunoPrecipitation associated to high-throughput sequencing (CLIP-seq) coupled with bioinformatics analysis to comprehensively uncover the miRNA targetome skew in prostate cancer using cell lines models for androgen dependency growth and primary tumors

Aims:

1. IDENTIFICATION OF THE ANDROGEN-DEPENDENT MIRNA TARGETOME IN PROSTATE CANCER CELL LINES

2. INVESTIGATION OF THE TARGET SEQUENCE MICROENVIRONMENT OF ANDROGEN-DEPENDENT MIRNA TARGETOME IN PROSTATE CANCER CELLS

3. IDENTIFICATION OF THE MIRNA TARGETOME IN PROSTATE CANCER BIOPSIES

Experience in gene expression, bioinformatics, and especially in next-generation sequencing analysis and programming (i.e. Computational Biologist) is highly desirable

"

- If you are interested please email to Michele Trabucchi your CV accompanied by at least one reference letter

Michele Trabucchi, PhD

Control of Gene Expression

INSERM U 1065, C3M

University of Nice Sophia-Antipolis

151, route de St-Antoine-de-Ginestière

B.P. 2 3194

06204 - NICE CEDEX 3

France

Phone +33-489-0642-56 (80)

Fax +33-489-0642-60

e-Mail: michele.trabucchi@unice.fr

http://www.unice.fr/c3m/index.php/research-teams/michele-trabucchi/