miRNAs are a key component of the noncoding RNA family. The underlying mechanisms involved in the interplay between the tumor microenvironment and cancer cells involve highly dynamic factors such as hypoxia and cell types such as cancer-associated fibroblasts and macrophages. Although miRNA levels are known to be altered in cancer cells, recent evidence suggests a critical role for the tumor microenvironment in regulating miRNA biogenesis, methylation, and transcriptional changes. Here, we discuss the complex protumorigenic symbiotic role between tumor cells, the tumor microenvironment, and miRNA deregulation.
Significance: miRNAs play a central role in cell signaling and homeostasis. In this article, we provide insights into the regulatory mechanisms involved in the deregulation of miRNAs in cancer cells and the tumor microenvironment and discuss therapeutic intervention strategies to overcome this deregulation. Cancer Discov; 6(3); 1–11. ©2016 AACR.
- Received July 23, 2015.
- Revision received October 16, 2015.
- Accepted October 19, 2015.
- ©2016 American Association for Cancer Research.