| First Author | Riemondy K | Year | 2015 |
| Journal | Elife | Volume | 4 |
| PubMed ID | 26203562 | Mgi Jnum | J:226044 |
| Mgi Id | MGI:5695699 | Doi | 10.7554/eLife.07004 |
| Citation | Riemondy K, et al. (2015) MicroRNA-203 represses selection and expansion of oncogenic Hras transformed tumor initiating cells. Elife 4 |
| abstractText | In many mouse models of skin cancer, only a few tumors typically form even though many cells competent for tumorigenesis receive the same oncogenic stimuli. These observations suggest an active selection process for tumor-initiating cells. Here, we use quantitative mRNA- and miR-Seq to determine the impact of Hras(G12V) on the transcriptome of keratinocytes. We discover that microRNA-203 is downregulated by Hras(G12V). Using a knockout mouse model, we demonstrate that loss of microRNA-203 promotes selection and expansion of tumor-initiating cells. Conversely, restoration of microRNA-203 using an inducible model potently inhibits proliferation of these cells. We comprehensively identify microRNA-203 targets required for Hras-initiated tumorigenesis. These targets include critical regulators of the Ras pathway and essential genes required for cell division. This study establishes a role for the loss of microRNA-203 in promoting selection and expansion of Hras mutated cells and identifies a mechanism through which microRNA-203 antagonizes Hras-mediated tumorigenesis. |
