miR‐450a exerts oncosuppressive effects in breast carcinoma by targeting CREB1

Abstract

Abstract Emerging evidence greatly implicates that microRNA‐450a (miR‐450a) plays an essential role in cancer pathobiology. While the pathological role of miR‐450a in breast carcinogenesis remains enigmatic. Herein, we showed that miR‐450a was lowly expressed in breast cancer cell lines compared with normal, and low miR‐450a expression was associated with poor survival in patients with breast cancer. We revealed that miR‐450a mimic transfected breast cancer cells (T47D and BT474) exhibited attenuated capacities of proliferation, migration, and invasion in vitro, and miR‐450a suppressed T47D cell growth in a xenograft tumor model. Mechanistically, cAMP response element‐binding protein 1 (CREB1) was negatively targeted by miR‐450a, and CREB1 deletion mimicked the effects of miR‐450a mimic treatment. Bioinformatics analysis further revealed that elevated expression of CREB1 correlated with poor prognosis in patients with breast cancer and miR‐450a level was negatively correlated with CREB1 level in breast cancer. Additionally, miR‐450a inhibited the phosphorylation of phosphatidylinositol 3‐kinase/V‐akt murine thymoma viral oncogene homolog (PI3K/AKT) and the activities of matrix metalloproteinase‐2/9 (MMP‐2/9). The following rescue assay indicated that CREB1 was implicated in the anti‐tumoral effect of mR‐450a in breast carcinoma. All these observations disclosed that miR‐450a negatively regulates the growth and metastatic property of breast carcinoma cells.

Keywords

• breast cancer
• CREB1
• invasion
• migration
• MiR‐450a