| First Author | Salmanidis M | Year | 2013 |
| Journal | Cell Death Differ | Volume | 20 |
| Issue | 10 | Pages | 1370-80 |
| PubMed ID | 23872792 | Mgi Jnum | J:228606 |
| Mgi Id | MGI:5708012 | Doi | 10.1038/cdd.2013.92 |
| Citation | Salmanidis M, et al. (2013) Hoxb8 regulates expression of microRNAs to control cell death and differentiation. Cell Death Differ 20(10):1370-80 |
| abstractText | Hoxb8 overexpression immortalises haematopoietic progenitor cells in a growth-factor-dependant manner and co-operates with interleukin-3 (IL-3) to cause acute myeloid leukaemia. To further understand how Hoxb8 contributes to myeloid cell immortalisation, we generated IL-3-dependant myeloid cells expressing Hoxb8 under the control of an inducible promoter. Downregulation of Hoxb8, in the presence of IL-3, caused cell-cycle arrest and apoptosis in the majority of cells. Apoptosis was dependant on Bax and Bak and, in part, on Bim, which was repressed by Hoxb8. Deletion of the miR-17 approximately 92 seed sequences in the Bim 3'UTR abolished Hoxb8-dependant regulation of Bim reporter constructs. Expression of all six miRNAs from this cluster were elevated when Hoxb8 was overexpressed. The miR-17 approximately 92 cluster was required for repression of Bim in Hoxb8-immortalised cells and deletion of the miR-17 approximately 92 cluster substantially inhibited Hoxb8, but not Hoxa9, mediated survival and proliferation. Hoxb8 appears to promote miR-17 approximately 92 expression through c-Myc, a known transcriptional regulator of the miR-17 approximately 92 cluster. We have uncovered a previously unrecognised link between Hoxb8 expression and microRNAs that provides a new insight into the oncogenic functions of Hoxb8. |
