MicroRNA profiling in isogenic models of cellular transformation involving either breast epithelial cells or fibroblasts reveals that expression of miR-193a is lower in transformed cells than in non-tranformed cells. The transcription factors RXRα and Max bind directly to the miR-193a promoter and inhibit miR-193a expression during transformation. MiR-193a inhibits cellular transformation by directly targeting the 3'UTRs of PLAU and K-Ras. Interestingly, miR-193a controls anchorage-independent growth in soft agar through K-Ras, while it affects invasive growth through PLAU. MiR-193a overexpression inhibits the tumorigenicity of developmentally diverse, but not all cancer cell types, and it inhibits tumor growth in colon- and breast-derived xenografts. Lastly, expression of miR-193a is inversely correlated with PLAU and K-Ras in human colon adenocarcinomas. Thus, a pathway in which Max and RXRα inhibit miR-193a expression, thereby activating the PLAU and K-Ras oncogenes is important for distinct aspects of cellular transformation, as well as tumor growth and colon (and perhaps other types of) cancer.
- Received February 4, 2011.
- Revision received May 4, 2011.
- Accepted June 6, 2011.
- Copyright © 2011, American Association for Cancer Research.