Aberrant microRNA (miRNA) expression has been identified in various human solid cancers. However, whether the levels of miRNA expression in tumor cells have any effect on tumor progression has not been determined. In this proof-of-concept study, the restoration of high-level expression of the miR17–92 cluster of miRNAs reveals its function as a tumor suppressor in murine solid cancer cells. Specifically, genetically engineered expression of higher levels of miR17/20a in the miR17–92 cluster in both murine breast cancer and colon cancer cells triggered natural killer (NK)–cell recognition by inhibiting the expression of MHC class I (H-2D) through the Mekk2–Mek5–Erk5 pathway. Results from the mouse tumor studies were recapitulated using samples of human solid tumors. Together, these data indicate that miR17/20a miRNAs function as tumor suppressors by reprogramming tumor cells for NK cell-mediated cytotoxicity. Cancer Immunol Res; 2(8); 1–11. ©2014 AACR.
Note: Supplementary data for this article are available at Cancer Immunology Research Online (http://cancerimmunolres.aacrjournals.org/).
- Received September 24, 2013.
- Revision received March 29, 2014.
- Accepted April 24, 2014.
- ©2014 American Association for Cancer Research.