MicroRNA-182 down-regulates the expression of MTSS1 and promotes the migration and metastasis of three-negative breast cancer / 医学研究生学报

ABSTRACT

Objective The up-regulated expression of miR-182 is associated with poor prognosis of triple-negative breast cancer. This study explored the biological function of the miR-182/MTSS1 signaling pathway in three-negative breast cancer (TNBC) and the mechanism of its regulation. Methods The relative quantitative expressions of miR-182 and MTSS1 were detected in the cancerous and adjacent tissues of 30 cases of TNBC, the influence of miR-182 and MTSS1 on the proliferation and invasiveness of the cells evaluated by cell function tests, the potential binding sites of miR-182 to MTSS1 predicted with the Targetscan software, and MTSS1 confirmed to be the target gene by the dual luciferase reporter system. After transfection of miR-182 into the MCF-7 cells, RT-PCR and Western blot were used to determine the gene and protein expressions of MTSS1 and verify the regulatory effect of miR-182 targeting MTSS1. Results The expression of miR-182 was significantly higher (t=-8.409, P=0.000), while that of MTSS1 lower in the cancerous than in the adjacent tissue (t=2.961, P=0.006). The over expression of miR-182 and silenced expression of MTSS1 markedly enhanced the proliferation and migration of the MCF-7 cells compared with those of the control (P<0.01), while inhibition of miR-182 and over expression of MTSS1 remarkably suppressed their proliferation and migration of the MDA-MB-231 cells (P<0.01). The base sequences of 1083-1089 of the MTSS1 gene were confirmed to be the target binding sites of miR-182. After transfection of miR-182, the expression of MTSS1 in the MCF-7 cells was significantly down-regulated as compared with that in the control (t=-5.918, P= 0.027). Conclusion Target binding of miR-182 to MTSS1 down-regulates the expression of MTSS1 and promotes cell proliferation and migration, which may play an important biological role in the metastasis of TNBC.