MicroRNA-708-3p mediates metastasis and chemoresistance through inhibition of epithelial-to-mesenchymal transition in breast cancer.

Metastasis and chemoresistance remain major challenges in the clinical treatment of breast cancer. Recent studies show that dysregulated microRNAs (miRNAs) play an important role in metastasis and chemoresistance development in breast cancer. Herein, we identified downregulated expression of miR-708-3p in breast cancers. In particular, miR-708-3p expression was significantly decreased in specimens from breast cancer patients with metastasis compared to that in specimens from patients with no metastasis. Consistent with clinical data, our in vitro data show that miR-708-3p was more significantly decreased in invasive breast cancer cell lines. In addition, our data show that inhibition of miR-708-3p significantly stimulated breast cancer cell metastasis and induced chemoresistance both in vitro and in vivo. In contrast, overexpression of miR-708-3p dramatically inhibited breast cancer cell metastasis and enhanced the sensitivity of breast cancer cells to chemotherapy both in vitro and in vivo. Furthermore, we identified that miR-708-3p inhibits breast cancer cell epithelial-to-mesenchymal transition (EMT) by directly targeting EMT activators, including ZEB1, CDH2 and vimentin. Taken together, our findings suggest that miR-708-3p acts as a cancer suppressor miRNA and carries out its anticancer function by inhibiting EMT in breast cancer. In addition, our findings suggest that restoration of miR-708-3p may be a novel strategy for inhibiting breast cancer metastasis and overcoming the chemoresistance of breast cancer cells.

miR-1307-3p Stimulates Breast Cancer Development and Progression by Targeting SMYD4.

Recent studies show that dysregulated miRNAs play an important role in breast cancer initiation and progression. Here, we identified upregulated expression of miR-1307-3p in breast cancer tissues and that increased level of miR-1307-3p was closely correlated with lower survival rate in breast cancer patients. Consistent with clinical data, our in vitro data show that expression level of miR-1307-3p was significantly increased in breast cancer cell lines compared to human mammary epithelial cell line MCF10A. Overexpression of miR-1307-3p in MCF10A stimulated cell proliferation and caused their growth in soft agar and tumor formation in nude mice. In contrast, inhibition of miR-1307-3p suppressed breast cancer cell proliferation and their growth in soft agar and inhibited tumor formation in nude mice. Further, we identified that miR-1307-3p plays its oncogenic role through targeting SET and MYND domain-containing 4 (SMYD4) expression in breast cancer. Taken together, our findings suggest that miR-1307-3p is a oncogenic miRNA that significantly contributes to breast cancer development and progression, and inhibition of miR-1307-3p may be a novel strategy for inhibits breast cancer initiation and progression.