Reference : Identification of a microRNA landscape targeting the PI3K/Akt signaling pathway in in...
Scientific journals : Article
Human health sciences : Oncology
http://hdl.handle.net/2268/164117
Identification of a microRNA landscape targeting the PI3K/Akt signaling pathway in inflammation-induced colorectal carcinogenesis
English
JOSSE, Claire [Centre Hospitalier Universitaire de Liège - CHU > > Oncologie médicale >]
Bouznad, Nassim [Université de Liège - ULg > Département des Sciences Biomédicales et Précliniques > GIGA-R: Génétique Humaine, Laboratoire de Thrombose Hémostase > >]
Geurts, Pierre [Université de Liège - ULg > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Algorith. des syst. en interaction avec le monde physique >]
Irrthum, Alexandre [Université de Liège - ULg > Département d'électricité, électronique et informatique > > >]
Huynh-Thu, Vân Anh [Université de Liège - ULg > > GIGA-Management : Coordination ALMA-GRID >]
Servais, Laurence [Université de Liège - ULg > Département des Sciences Biomédicales et Précliniques > GIGA-R: Génétique Humaine, Laboratoire de Thrombose Hémostase > GIGA - Membres >]
Hego, Alexandre [Université de Liège - ULg > Département des Sciences Biomédicales et Précliniques > GIGA-R : Génétique Humaine, Laboratoire de Thrombose Hémostase > >]
Delvenne, Philippe [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Bours, Vincent [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine >]
Oury, Cécile mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine, Laboratoire de Thrombose Hémostase > >]
2014
American Journal of Physiology - Gastrointestinal and Liver Physiology
American Physiological Society
306
G229-43
Yes (verified by ORBi)
International
0193-1857
1522-1547
[en] Inflammation can contribute to tumor formation; however, markers that predict progression are still lacking. In the present study, the well-established azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model of colitis-associated cancer was used to analyze microRNA (miRNA) modulation accompanying inflammation-induced tumor development and to determine whether inflammation-triggered miRNA alterations affect the expression of genes or pathways involved in cancer. A miRNA microarray experiment was performed to establish miRNA expression profiles in mouse colon at early and late time points during inflammation and/or tumor growth. Chronic inflammation and carcinogenesis were associated with distinct changes in miRNA expression. Nevertheless, prediction algorithms of miRNA-mRNA interactions and computational analyses based on ranked miRNA lists consistently identified putative target genes that play essential roles in tumor growth or that belong to key carcinogenesis-related signaling pathways. We identified PI3K/Akt and the insulin growth factor-1 (IGF-1) as major pathways being affected in the AOM/DSS model. DSS-induced chronic inflammation downregulates miR-133a and miR-143/145, which is reportedly associated with human colorectal cancer and PI3K/Akt activation. Accordingly, conditioned medium from inflammatory cells decreases the expression of these miRNA in colorectal adenocarcinoma Caco-2 cells. Overexpression of miR-223, one of the main miRNA showing strong upregulation during AOM/DSS tumor growth, inhibited Akt phosphorylation and IGF-1R expression in these cells. Cell sorting from mouse colons delineated distinct miRNA expression patterns in epithelial and myeloid cells during the periods preceding and spanning tumor growth. Hence, cell-type-specific miRNA dysregulation and subsequent PI3K/Akt activation may be involved in the transition from intestinal inflammation to cancer.
Researchers
http://hdl.handle.net/2268/164117
10.1152/ajpgi.00484.2012

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