Tumor-promoting properties of miR-8084 in breast cancer through enhancing proliferation, suppressing apoptosis and inducing epithelial-mesenchymal transition.

BACKGROUND

Breast cancer is one of the most frequent malignancies and the second leading cause of cancer-related mortality in women. MicroRNAs play a key role in breast cancer development and progression. microRNA(miR)-8084 has been observed an aberrant expression in breast cancer. However, the functions and regulatory axes of miR-8084, particularly in breast cancer, were not entirely clear.

METHODS

miR-8084 expression in breast cancer were investigated in a GEO dataset by in silico analysis and in 42 paired tumor tissues by qPCR. The effects of deregulation of miR-8084 on breast cancer cell proliferation, migration and invasion in vitro and tumorigenicity in vivo were examined by colony-formation assay, wound healing assay, transwell assay and nude mouse subcutaneous tumor formation model. The target gene of miR-8084 were predicted by TargetScan and miRDB, and confirmed by luciferase reporter system. The roles of miR-8084 in the breast cancer cell proliferation, apoptosis and epithelial-mesenchymal transition (EMT) were investigated by MTS, FACS and associated-marker detection by western blot.

RESULTS

miR-8084 is significantly up-regulated in both serum and malignant tissues from the source of breast cancer patients. miR-8084 promotes the proliferation of breast cancer cells by activating ERK1/2 and AKT. Meanwhile miR-8084 inhibits apoptosis by decreasing p53-BAX related pathway. miR-8084 also enhances migration and invasion by inducing EMT. Moreover, the tumor suppressor ING2 is a potential target of miR-8084, and miR-8084 regulatory axes contribute to pro-tumor effect, at least partially through regulating ING2.

CONCLUSION

Our results strongly suggest that miR-8084 functions as an oncogene that promotes the development and progression of breast cancer, and miR-8084 is a potential new diagnostic marker and therapeutic target of breast cancer.