MicroRNAs play a big role in regulating ovarian cancer-associated fibroblasts and the tumor microenvironment

Abstract

Mitra and colleagues analyzed microRNA expression profiles of fibroblasts isolated from ovarian cancer patients, searching for dysregulated microRNAs in the stromal compartment of human cancer. They found that decreased miR-31 and miR-214 and increased miR-155 expression can reprogram normal fibroblasts into tumor-promoting cancer-associated fibroblasts. They identified CCL5, a protumorigenic chemokine that is highly expressed in tumors, as a key target of miR-214, thus showing that microRNA perturbation in the stromal microenvironment can affect tumor growth.

Figure 1

Summary of the experimental strategy and key findings in Mitra et al. (10). The authors isolated cancer-associated fibroblasts (CAFs) and adjacent normal fibroblasts from ovarian cancer patients, and looked for differentially expressed microRNAs using microarrays. They found increased expression of miR-155 and decreased expression of miR-214 and miR-31 in CAFs. Perturbation of these microRNAs was sufficient to generate induced CAFs from normal fibroblasts. One key target of miR-214 was CCL5, which provided tumor-promoting signals back to the carcinoma cells. The tumor-derived signals that regulate expression of these microRNAs remain to be determined, as well as effects on other components of the tumor microenvironment.