MicroARN et physiopathologie intestinale

MicroRNAs and intestinal pathophysiology

Inserm, U773, Centre de Recherche Bichat Beaujon CRB3, BP 416, F-75870, Paris, France.
Université Paris 7 Denis Diderot, site Bichat, BP 416, F-75018, Paris, France

^* Eric.Ogier-Denis@bichat.inserm.fr

Résumé

Les microARN (miARN) constituent une classe de petits ARN non codants d’environ 20 nucléotides qui contrôlent négativement l’expression d’ARN messagers cibles. Les eucaryotes multicellulaires utilisent les miARN pour contrôler leurs fonctions vitales, différenciation, prolifération ou apoptose. La diversité des miARN et le nombre considérable de leurs ARN messagers cibles en font des acteurs importants de la régulation de l’expression génique. Des études récentes ont révélé que l’expression anormale des miARN représente une caractéristique commune des cellules cancéreuses et que ces miARN peuvent fonctionner comme des gènes suppresseurs de tumeur ou des oncogènes. Cette revue fait le point des travaux portant sur l’implication des miARN dans la pathogénie des cancers colorectaux. Le rôle des miARN dans le contrôle de l’inflammation et leur implication potentielle dans les pathologies inflammatoires intestinales sont aussi discutés.

Abstract

MicroRNAs (miRNAs) represent an abundant class of endogenously expressed small RNAs, which is believed to control the expression of proteins through specific interaction with their mRNAs. MiRNAs are non-coding RNAs of 18 to 24 nucleotides that negatively regulate target mRNAs by binding to their 3’-untranslated regions (UTR). Most eukaryotic cells utilize miRNA to regulate vital functions such as cell differentiation, proliferation or apopotosis. The diversity of miRNAs and of their mRNA targets strongly indicate that they play a key role in the regulation of protein expression. To date, more than 500 different miRNAs have been identified in animals and plants. There are at least 326 miRNAs in the human genome, comprising 1-4% of all expressed human genes, which makes miRNAs one of the largest classes of gene regulators. A single miRNA can bind to and regulate many different mRNA targets and, conversely, several different miRNAs can bind to and cooperatively control a single mRNA target. The correlation between the expression of miRNAs and their effects on tumorigenesis and on the proliferation of cancer cells is beginning to gain experimental evidences. Recent studies showed that abnormal expression of miRNAs represents a common feature of cancer cells and that they can function as tumor suppressor genes or as oncogenes. Therefore, this diversity of action for miRNAs on several target genes could be one of the common mechanisms involved in the deregulation of protein expression observed during intestinal disorders. In this review, the emergent functions of miRNAs in colorectal cancer and their potential role in the intestinal inflammatory process are discussed.