title: Cooperative control of tumor suppressor genes by a network of oncogenic microRNAs.
abstract: Individual microRNAs (miRNAs) have been implicated as oncogenes in experimental cancer models and their expression may affect clinical outcomes. To gain a more comprehensive view of miRNA action in leukemia, we analyzed miRNA expression patters in T-cell leukemia ALL (T-ALL) and cross-referenced the results with an unbiased genetic screen and computational analyses.1 We found that multiple microRNAs contribute to leukmogenesis and act as multi-targeted regulators of several tumor suppressor genes. The oncomirs form a network of overlapping and partially redundant interactions that stabilize the malignant phenotype though coordinate repression of cellular failsafe programs. The emerging network pattern of oncomir action is distinct from the notion of single oncogenic 'driver' mutation. We will discuss experimental, diagnostic and therapeutic implications of this concept of miRNA action in cancer.
authors.affiliation: Cancer Biology & Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Konstantinos J
authors.initials: KJ
authors.lastname: Mavrakis
authors.forename: Christina S
authors.initials: CS
authors.lastname: Leslie
authors.forename: Hans-Guido
authors.initials: HG
authors.lastname: Wendel
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D004195:Disease Models, Animal; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism; D000073979:F-Box-WD Repeat-Containing Protein 7; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D016147:Genes, Tumor Suppressor; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513272:Fbxw7 protein, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D044767:Ubiquitin-Protein Ligases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse