Tumor suppressor let-7a inhibits breast cancer cell proliferation, migration and invasion by targeting MAGE-A1.

Abstract

Let-7 was one of the earliest discovered miRNAs and while it reportedly acts as a tumor suppressor in various solid tumors, its function in breast cancer has not been fully studied. Therefore, we examined let-7a and MAGE-A1 expression in breast tissues by qRT-PCR and found that let-7a expression significantly correlates with larger tumor size, higher histological grade (p<0.05) and is significantly lower in patients with Her-2-positive cancers and Ki-67 >14% (p=0.028 and p=0.023). MAGE-A1 expression incidence is 50.8% (33/65) and it inversely correlates with let-7a expression (p=0.008). let-7a inhibition of breast cancer cell proliferation, migration and invasion was also observed in in vitro cell culture experiments, and dual-luciferase reporter assays showed that melanoma-associated antigen A1 (MAGE-A1) was its target gene; the target comprised bases 451-457 of the 3'UTR region of the MAGE-A1 mRNA. RT-qPCR and Western blot analyses showed that let-7a inhibited MAGE-A1 expression at both the nucleic acid and protein levels. In our final co-transfection experiment, we targeted MAGE-A1 in a breast cancer cell line and observed that let-7a inhibited cell proliferation, migration and invasion. These combined results confirm that let-7a functions as a tumor suppressor by targeting MAGE-A1 in breast cancer and it therefore provides a novel target in breast cancer clinical treatment.