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Lenalidomide-mediated enhanced translation of C/EBP?-p30 protein upregulates expression of the anti-leukemic microRNA-181a in acute myeloid leukemia - microRNA Data

ABSTRACT: Recently, we showed that increased miR-181a expression was associated with improved outcomes in cytogenetically normal acute myeloid leukemia (CN-AML). Interestingly, miR-181a expression was increased in CN-AML patients harboring CEBPA mutations, which are usually biallelic and associate with better prognosis. CEBPA encodes the C/EBP? transcription factor. We demonstrate here that the presence of N-terminal CEBPA mutations and miR-181a expression are linked. Indeed, the truncated C/EBP?-p30 isoform, which is produced from the N-terminal mutant CEBPA gene or from the differential translation of wild-type CEBPA mRNA and is commonly believed to have no transactivation activity, binds to the miR-181a-1 promoter and upregulates the microRNA expression. In xenograft mouse models, ectopic miR-181a expression inhibits tumor growth. This regulatory pathway may explain an increased sensitivity to apoptosis-inducing chemotherapy in subsets of AML patients. Altogether, our data provide a potential explanation for the improved clinical outcomes observed in CEBPA-mutated CN-AML patients.

ORGANISM(S): Homo sapiens

SUBMITTER: Guido Marcucci

PROVIDER: E-MTAB-1320 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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