UCAGenomiX related publications

Du to our strong expertise in "omics" experiments and in microRNAs topics we decided to separate into 3 categories the related publications into which the Functional genomics Platform of Nice-Sophia-Antipolis is involved :
  1. Expression studies (DNA microarrays and high-throughput sequencing experiments)
  2. MicroRNA studies
  3. Miscellaneous

Moreno-Leon Laura

 moreno@ipmc.cnrs.fr
 04 93 95 77 91
 660 route des lucioles 06560 Valbonne - Sophia-Antipolis

1 publications found

1. Tissue inhibitor of metalloproteinases-1 induces a pro-tumourigenic increase of miR-210 in lung adenocarcinoma cells and their exosomes.
Oncogene. 2014 Sep 29. doi: 10.1038/onc.2014.300.
Cui H, Seubert B, Stahl E, Dietz H, Reuning U, Moreno-Leon L, Ilie M, Hofman P, Nagase H, Mari B, Krüger A
1Institut für Experimentelle Onkologie und Therapieforschung, Klinikum Rechts der Isar der Technischen Universität München, Ismaninger Straße 22, Munich, Germany. 2Physik Department, Walter Schottky Institute, Technische Universität München, Am Coulombwall 4a, Munich, Germany. 3Klinische Forschergruppe der Frauenklinik, Klinikum Rechts der Isar der Technischen Universität München, Ismaninger Straße 22, Munich, Germany. 41] University of Nice Sophia-Antipolis, Nice, France [2] Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, UMR 6097 CNRS/UNSA, Sophia Antipolis, France. 51] University of Nice Sophia-Antipolis, Nice, France [2] Laboratory of Clinical and Experimental Pathology and Hospital Integrated Biobank, Centre Hospitalier Universitaire de Nice, Nice, France. 6Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Muscolosketal Sciences, University of Oxford, London, UK.

Tissue inhibitor of metalloproteinases-1 (TIMP-1) recently emerged as a pro-metastatic factor highly associated with poor prognosis in a number of cancers. This correlation seemed paradox as TIMP-1 is best described as an inhibitor of pro-tumourigenic matrix metalloproteinases. Only recently, TIMP-1 has been revealed as a signalling molecule that can regulate cancer progression independent of its inhibitory properties. In the present study, we demonstrate that an increase of both exogenous and endogenous TIMP-1 led to the upregulation of miR-210 in a CD63/PI3K/AKT/HIF-1-dependent pathway in lung adenocarcinoma cells. TIMP-1 induced P110/P85 PI3K-signalling and AKT phosphorylation. It also led to increase of HIF-1α protein levels positively correlating with HIF-1-regulated mRNA expression and upregulation of the microRNA miR-210. Downstream targets of miR-210, namely FGFRL1, E2F3, VMP-1, RAD52 and SDHD, were decreased in the presence of TIMP-1. Upon the overexpression of TIMP-1 in tumour cells, miR-210 was accumulated in exosomes in vitro and in vivo. These exosomes promoted tube formation activity in human umbilical vein endothelial cell (HUVECs), which was reflected in increased angiogenesis in A549L-derived tumour xenografts. Activation and elevation of PI3K, AKT, HIF-1A and miR-210 in tumours additionally confirmed our in vitro data. This new pro-tumourigenic signalling function of TIMP-1 may explain why elevated TIMP-1 levels in lung cancer patients are highly correlated with poor prognosis.Oncogene advance online publication, 29 September 2014; doi:10.1038/onc.2014.300.
Pubmed link : 25263437