Daschkey, Svenja and Roettgers, Silja and Giri, Anamika and Bradtke, Jutta and Teigler-Schlegel, Andrea and Meister, Gunter and Borkhardt, Arndt and Landgraf, Pablo (2013) MicroRNAs Distinguish Cytogenetic Subgroups in Pediatric AML and Contribute to Complex Regulatory Networks in AML-Relevant Pathways. PLOS ONE, 8 (2): e56334. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Background: The role of microRNAs (miRNAs), important post-transcriptional regulators, in the pathogenesis of acute myeloid leukemia (AML) is just emerging and has been mainly studied in adults. First studies in children investigate single selected miRNAs, however, a comprehensive overview of miRNA expression and function in children and young adults is missing so far. Methodology/Principal Findings: We here globally identified differentially expressed miRNAs between AML subtypes in a survey of 102 children and adolescent. Pediatric samples with core-binding factor AML and promyelocytic leukemia could be distinguished from each other and from MLL-rearranged AML subtypes by differentially expressed miRNAs including miR-126, -146a, -181a/b, -100, and miR-125b. Subsequently, we established a newly devised immunoprecipitation assay followed by rapid microarray detection for the isolation of Argonaute proteins, the hallmark of miRNA targeting complexes, from cell line models resembling core-binding factor and promyelocytic leukemia. Applying this method, we were able to identify Ago-associated miRNAs and their targeted mRNAs. Conclusions/Significance: miRNAs as well as their mRNA-targets showed binding preferences for the different Argonaute proteins in a cell context-dependent manner. Bioinformatically-derived pathway analysis suggested a concerted action of all four Argonaute complexes in the regulation of AML-relevant pathways. For the first time, to our knowledge, a complete AML data set resulting from carefully devised biochemical isolation experiments and analysis of Ago-associated miRNAs and their target-mRNAs is now available.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACUTE MYELOID-LEUKEMIA; GENE-EXPRESSION; RIBONUCLEOPROTEIN COMPLEXES; WIDE IDENTIFICATION; C/EBP-ALPHA; RIP-CHIP; PROTEIN; DIFFERENTIATION; PATTERNS; ASSOCIATION; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Apr 2020 06:54 |
| Last Modified: | 24 Apr 2020 06:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17151 |
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