Coordinated expression of microRNA-155 and predicted target genes in diffuse large B-cell lymphoma.
MicroRNAs (miRNAs) attenuate gene expression by pairing to the 3'UTR of target transcripts inducing RNA cleavage or translational inhibition. Overexpression of microRNA-155 (miR-155), measured either at the primary (BIC gene) or mature transcript level, was recently described in diffuse large B-cell lymphomas (DLBCL). These studies have been limited in size, however, and have not attempted to link miR-155 expression to that of putative target genes. To start to address these issues, we examined a collection of 22 well-characterized DLBCL cell lines. The expression of miR-155 is heterogeneous in these cell lines and associates with NF-kappaB activity. We found that the expression of the primary miR-155 transcript reliably reflects that of the functional mature miR-155. Because many gene array platforms include probe sets for the primary miR-155 sequences, these findings allowed us to confidently examine large array-based expression datasets of primary DLBCLs in the context of miR-155 levels. Our investigation revealed that miR-155 expression segregates with specific molecular subgroups of DLBCL and it is highest in activated B-cell (ABC)-type lymphomas. These tumors are characterized by constitutive activation of NF-kappaB signals, which supports the data derived from our cell lines. More importantly, using supervised learning algorithms, we identified a robust gene signature driven by the differential expression of miR-155. These profiles contained several gene markers, including predicted targets, consistently downregulated in tumors expressing high levels of miR-155. Our data start to unveil the genome-wide effects of miR-155 expression in DLBCL and indicate the utility of this strategy in the identification and validation of miRNA target genes.
Rai
Deepak
D
Division of Hematology and Medical Oncology, Department of Medicine, San Antonio Cancer Institute, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC7880, San Antonio, TX 78229, USA.
Karanti
Shailaja
S
Jung
Inkyung
I
Dahia
Patricia L M
PL
Aguiar
Ricardo C T
RC
D015152:Blotting, Northern; D045744:Cell Line, Tumor; D003470:Culture Media; D005786:Gene Expression Regulation; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics* / Q000302:isolation & purification; D016328:NF-kappa B / Q000378:metabolism; D015347:RNA Probes; D012334:RNA, Neoplasm / Q000235:genetics* / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D003470:Culture Media; D035683:MicroRNAs; D016328:NF-kappa B; D015347:RNA Probes; D012334:RNA, Neoplasm