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.

MicroRNA-142 is mutated in about 20% of diffuse large B-cell lymphoma / Wiyada, Kwanhian; Dido, Lenze; Julia, Alles; Natalie, Motsch; Stephanie, Barth; Celina, Doll; Jochen, Imig; Michael, Hummel; Marianne, Tinguely; Trivedi, Pankaj; Viraphong, Lulitanond; Gunter, Meister; Christoph, Renner; Friedrich A., Grasser. - In: CANCER MEDICINE. - ISSN 2045-7634. - STAMPA. - 1:2(2012), pp. 141-155. [10.1002/cam4.29]

MicroRNA-142 is mutated in about 20% of diffuse large B-cell lymphoma.

TRIVEDI, PANKAJ;
2012

Abstract

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.
2012
01 Pubblicazione su rivista::01a Articolo in rivista
MicroRNA-142 is mutated in about 20% of diffuse large B-cell lymphoma / Wiyada, Kwanhian; Dido, Lenze; Julia, Alles; Natalie, Motsch; Stephanie, Barth; Celina, Doll; Jochen, Imig; Michael, Hummel; Marianne, Tinguely; Trivedi, Pankaj; Viraphong, Lulitanond; Gunter, Meister; Christoph, Renner; Friedrich A., Grasser. - In: CANCER MEDICINE. - ISSN 2045-7634. - STAMPA. - 1:2(2012), pp. 141-155. [10.1002/cam4.29]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/517673
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