Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181.
B-cell chronic lymphocytic leukemia (B-CLL) is the most common human leukemia in the world. Deregulation of the TCL1 oncogene is a causal event in the pathogenesis of the aggressive form of this disease as was verified by using animal models. To study the mechanism of Tcl1 regulation in CLL, we carried out microRNA expression profiling of three types of CLL: indolent CLL, aggressive CLL, and aggressive CLL showing 11q deletion. We identified distinct microRNA signatures corresponding to each group of CLL. We further determined that Tcl1 expression is regulated by miR-29 and miR-181, two microRNAs differentially expressed in CLL. Expression levels of miR-29 and miR-181 generally inversely correlated with Tcl1 expression in the CLL samples we examined. Our results suggest that Tcl1 expression in CLL is, at least in part, regulated by miR-29 and miR-181 and that these microRNAs may be candidates for therapeutic agents in CLLs overexpressing Tcl1.
Pekarsky
Yuri
Y
Comprehensive Cancer Center, Human Cancer Genetics Program and Department of Molecular Virology, Immunology, and Medical Genetics, OSU School of Medicine, Ohio State University, Columbus, Ohio 43210, USA. Pekarsky.Yuri@osumc.edu
Santanam
Urmila
U
Cimmino
Amelia
A
Palamarchuk
Alexey
A
Efanov
Alexey
A
Maximov
Vadim
V
Volinia
Stefano
S
Alder
Hansjuerg
H
Liu
Chang-Gong
CG
Rassenti
Laura
L
Calin
George A
GA
Hagan
John P
JP
Kipps
Thomas
T
Croce
Carlo M
CM
D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics*
C526366:MIRN29 microRNA, rat; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C090851:TCL1A protein, human