The role of microRNA and other non-coding RNA in the pathogenesis of chronic lymphocytic leukemia.
New findings support the view that chronic lymphocytic leukemia (CLL) is a genetic disease in which the main alterations occur in a new class of genes named microRNAs (miRNAs). Cases with good prognostic features typically are characterized by miRNA down-regulation of genes miR-15a and miR-16-1, located at 13q14.3. Both microRNAs negatively regulate BCL2 at a post-transcriptional level. On the other hand, in CLL cases that use unmutated immunoglobulin heavy-chain variable-region genes (IgV(H)) or have high-level expression of the 70-kD zeta-associated protein (ZAP-70) have high levels of TCL1 due to low-level expression of miR-29 and miR-181, which directly target this oncogene. Conceivably, these miRNAs might be used to target BCL2 or TCL1 for therapy of this disease.
Calin
George A
GA
Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Wiseman Hall Room 385K, 400 12th Avenue, Ohio State University, Columbus, OH 43210, USA.
Pekarsky
Yuri
Y
Croce
Carlo M
CM
D000818:Animals; D015536:Down-Regulation; D019254:Genes, bcl-2 / Q000235:genetics; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics
C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C090851:TCL1A protein, human