MicroRNA-142 is mutated in about 20% of diffuse large B-cell lymphoma.
MicroRNAs (miRNAs) are short 18-23 nucleotide long noncoding RNAs that posttranscriptionally regulate gene expression by binding to mRNA. Our previous miRNA profiling of diffuse large B-cell lymphoma (DLBCL) revealed a mutation in the seed sequence of miR-142-3p. Further analysis now showed that miR-142 was mutated in 11 (19.64%) of the 56 DLBCL cases. Of these, one case had a mutation in both alleles, with the remainder being heterozygous. Four mutations were found in the mature miR-142-5p, four in the mature miR-142-3p, and three mutations affected the miR-142 precursor. Two mutations in the seed sequence redirected miR-142-3p to the mRNA of the transcriptional repressor ZEB2 and one of them also targeted the ZEB1 mRNA. However, the other mutations in the mature miR-142-3p did not influence either the ZEB1 or ZEB2 3' untranslated region (3' UTR). On the other hand, the mutations affecting the seed sequence of miR-142-3p resulted in a loss of responsiveness in the 3' UTR of the known miR-142-3p targets RAC1 and ADCY9. In contrast to the mouse p300 gene, the human p300 gene was not found to be a target for miR-142-5p. In one case with a mutation of the precursor, we observed aberrant processing of the miR-142-5p. Our data suggest that the mutations in miR-142 probably lead to a loss rather than a gain of function. This is the first report describing mutations of a miRNA gene in a large percentage of a distinct lymphoma subtype.
Institute of Virology, Saarland University Medical School 66421, Homburg, Germany; Department of Microbiology, Faculty of Medicine, Khon Kaen University 40002, Khon Kaen, Thailand.
Wiyada
W
Kwanhian
Dido
D
Lenze
Julia
J
Alles
Natalie
N
Motsch
Stephanie
S
Barth
Celina
C
Döll
Jochen
J
Imig
Michael
M
Hummel
Marianne
M
Tinguely
Pankaj
P
Trivedi
Viraphong
V
Lulitanond
Gunter
G
Meister
Christoph
C
Renner
Friedrich A
FA
Grässer
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D018398:Homeodomain Proteins; C555159:MIRN142 microRNA, human; D035683:MicroRNAs; C107953:RAC1 protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D020830:rac1 GTP-Binding Protein
Carcinogenesis; cellular biology; genomics; molecular genetics