Aberrant microRNA (miRNA) expression has been identified in various human solid cancers. However, whether the levels of miRNA expression in tumor cells have an effect on tumor progression has not been determined. In this proof of concept study, the restoration of high-level expression of the miR-17~92 cluster restores its function as a tumor suppressor in murine solid cancer cells. Specifically, higher levels of miR-17/20a in the miR-17~92 cluster in both murine breast cancer and colon cancer cells triggered NK cell recognition by inhibiting the expression of MHC class I (H2D) through the Mekk2/Mek5/Erk5 pathway. The results in mouse tumor studies were repeated using samples of human solid tumors. Together, these data reveal that miR-17/20a can function as a tumor-suppressor by reprogramming tumor cells to have high sensitivity to NK cell-mediated cytotoxicity.
- Received September 24, 2013.
- Revision received March 29, 2014.
- Accepted April 24, 2014.
- Copyright © 2014, American Association for Cancer Research.