MicroRNA-133a acts as a tumour suppressor in breast cancer through targeting LASP1.

Abstract

Many microRNAs (miRs) have been demonstrated to play promoting or tumor suppressive roles in human cancers including breast cancer. However, the molecular mechanism of miR-133a underlying the malignant progression of breast cancer still remains obscure. In the present study we observed that the expression of miR-133a was significantly downregulated in breast cancer tissues and cell lines, when compared with adjacent non-tumor tissues and normal breast cell line, respectively. Reduced miR-133a levels were significantly associated with advanced clinical stage, lymph node metastasis, as well as shorter survival time of patients with breast cancer. Restoration of miR-133a expression led to significant decrease in the proliferation, migration, and invasion of SK-BR-3 and MDA-MB-231 cells in vitro, as well as in tumor xenograft growth in nude mice. Luciferase reporter gene assay data identified LASP1 as a target gene of miR-133a, and the expression of LASP1 was negatively regulated by miR-133a in breast cancer cells. LASP1 was significantly upregulated in breast cancer tissues and cell lines, and its upregulation was significantly associated with disease progression. siRNA-induced LASP1 downregulation caused a significant reduction in breast cancer cell proliferation, migration and invasion. Furthermore, overexpression of LASP1 impaired the suppressive effects of miR-133a upregulation on the proliferation, migration and invasion of SK-BR-3 and MDA-MB-231 cells. In summary, the present study demonstrates that miR-133a acts as a tumor suppressor in breast cancer partly at least via targeting LASP1, and thus suggests that the miR-133a/LASP1 axis may become a potential therapeutic target for breast cancer.