Hsa_circ_002178 Promotes the Growth and Migration of Breast Cancer Cells and Maintains Cancer Stem-like Cell Properties Through Regulating miR-1258/KDM7A Axis

Abstract

Breast cancer (BrCa) is the most common malignancy in women. Accumulating evidence demonstrated that abnormal circRNA expression is associated with the occurrence and progression of tumors. We analyzed the GSE101123 data and found that the expression of hsa_circ_002178 (circ_002178) was significantly increased in BrCa tissues. However, the role and possible underlying mechanisms of circ_002178 in BrCa still remain unrevealed. In this investigation, the expression levels of circ_002178 in cancer tissues or BrCa cells were significantly upregulated compared with those in paracancer tissues or normal cells. High expression of circ_002178 was correlated with the low survival rate, clinical tumor size, lymph node metastasis, and tumor, nodes, and metastases grade. After microsphere culture, the expression of circ_002178 in SUM149PT and MDA-MB-231 cells was significantly increased. Further investigation exhibited that overexpression of circ_002178 contributed to the formation of microspheres, the elevated protein levels of stemness marker, and the increased activity of ALDH1 in SUM149PT cells. Besides, the overexpression of circ_002178 also significantly promoted the growth, invasion, and migration of BrCa cells. Correspondingly, the knockdown of circ_002178 showed the opposite result in MDA-MB-231 cells. Hsa_circ_002178 was further proved to downregulate the level of miR-1258 and reduce the inhibitory effect of miR-1258 on KDM7A, thus regulating the stem-like characteristics of BrCa cells and promoting the growth and migration of BrCa cells. Taken together, targeting the circ_002178/miR-1258/KDM7A axis may be a prospective strategy for the diagnosis and therapies of BrCa in the future.