MicroRNA-203 represses selection and expansion of oncogenic Hras transformed tumor initiating cells
Abstrak
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.
Penulis (5)
Kent Riemondy
Xiao-jing Wang
Enrique C Torchia
Dennis R Roop
Rui Yi
Akses Cepat
- Tahun Terbit
- 2015
- Bahasa
- en
- Total Sitasi
- 17×
- Sumber Database
- CrossRef
- DOI
- 10.7554/elife.07004
- Akses
- Open Access ✓