Down-regulation of miR-29b in carcinoma associated fibroblasts promotes cell growth and metastasis of breast cancer

Abstract

Carcinoma associated fibroblasts (CAFs) play important roles in breast cancer development and progression. Recent studies show that microRNAs (miRNAs) are the main regulators in CAFs. MiR-29b is one of the significant down-regulated miRNAs in CAFs from the miRNA screening. The role of miR-29b in the interaction between CAFs and breast cancer is still unclear. In the present study, we investigated the effects of CAFs on breast cancer cell proliferation and metastasis regulated by miR-29b. We found that fibroblasts activated by co-cultured breast cancer cells produced higher levels of some chemokines like CCL11, CXCL14, which accelerated breast cancer cell growth and induced drug resistance and metastasis. Increased miR-29b expression in activated fibroblasts could suppress the activating p38-STAT1 signal pathway in breast cancer cells. We also found that the expression of CCL11 and CXCL14 could be regulated by miR-29b in CAFs. Our results illustrate that down-regulation of miR-29b in CAFs plays an important role in tumor stroma by activating p38-STAT1 in breast cancer cells. The study indicates that cancer cells and fibroblasts interaction promotes breast cancer cell growth, drug resistance, migration and invasion due to the lack of miR-29b expression in CAFs.