MicroRNA29a regulates the expression of the nuclear oncogene Ski
Cette étude montre que le micro-ARN 29a joue un rôle important de suppresseur de tumeurs dans les leucémies myéloïdes aiguës en régulant l'expression de l'oncogène Ski
MicroRNAs (miRNAs) are small, non-coding RNA molecules regulating growth and differentiation. miRNAs are frequently located at cancer-specific fragile sites in the human genome, such as chromosome 7q. The nuclear oncogene Ski is up-regulated in acute myeloid leukemia (AML) with -7/del7q. Here we asked whether loss of miRNAs on chromosome 7q may explain this up-regulation. miR-29a expression was found down-regulated in AML with -7/del7q. Forced expression of miR-29a down-regulated Ski and its target gene Nr-CAM, whereas miR-29a inhibition induced Ski expression. Luciferase assays validated a functional binding site for miR-29a in the 3'UTR of Ski. Finally, in samples of AML patients, we observed an inverse correlation of Ski and miR-29a expression, respectively. In conclusion, up-regulation of Ski in AML with -7/del7q is caused by loss of miR-29a. miR-29a may therefore function as an important tumor suppressor in AML by restraining expression of the Ski oncogene.