Kwanhian, Wiyada and Lenze, Dido and Alles, Julia and Motsch, Natalie and Barth, Stephanie and Doell, Celina and Imig, Jochen and Hummel, Michael and Tinguely, Marianne and Trivedi, Pankaj and Lulitanond, Viraphong and Meister, Gunter and Renner, Christoph and Graesser, Friedrich A. (2012) MicroRNA-142 is mutated in about 20% of diffuse large B-cell lymphoma. CANCER MEDICINE, 1 (2). pp. 141-155. ISSN 2045-7634,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ; Carcinogenesis; cellular biology; genomics; molecular genetics |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 May 2020 05:00 |
| Last Modified: | 06 May 2020 05:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18075 |
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