miR-506 regulates breast cancer cell metastasis by targeting IQGAP1.

ABSTRACT

MicroRNA (miRNA or miR)-506 is a novel miRNA related to the survival of breast cancer patients. However, the mechanism underlying miRNA-506 involvement in breast carcinogenesis remains unclear. In the present study, we found that miR-506 was downregulated in human breast malignant tissues and breast cancer cell lines by RT-qPCR analysis, and the expression level of miR-506 was decreased with the increasing of tumor stage. Subsequently, gain-of-function and loss-of-function experiments were performed in vitro, and the results from MTT assay, Transwell-Matrigel invasion assay and cell adhesion assay revealed that miR-506 suppresses cell proliferation, invasion and adhesion of breast cancer cells. Luciferase reporter assay revealed that IQ motif containing GTPase activating protein 1 (IQGAP1) is a direct target of miR-506. miR-506 represses the expression of IQGAP1 and its downstream extracellular signal regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling pathways, as demonstrated by the RT-qPCR and western blot analysis. Furthermore, we found that IQGAP1 rescues the effect of miR-506 on cell proliferation, invasion, adhesion, and the activation of ERK MAPK signaling. In conclusion, the present study is the first to provide evidence that miR-506 acts as a tumor suppressor, at least partially, by directly downregulating IQGAP1 in breast cancer cells. The miR-506/IQGAP1/ERK pathway may be a novel therapeutic target in breast cancer.