[Hsa-miR-206 inhibits the migration and invasion of breast cancer by targeting Cx43].

ABSTRACT

OBJECTIVE: To explore the effects of hsa-miR-206 on the proliferation, migration and invasion of breast cancer. METHODS: The hsa-miR-206 mimics, inhibitors and their paired negative controls were transfected into human breast cancer cell line MDA-MB-231 by liposome. The proliferation of cell was evaluated by CCK-8 and the migration and invasion was detected by Transwell. Matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), breast cancer metastasis-suppressor 1 (BRMS-1) and connexin 43 (Cx43) were detected by both quantitative polymerase chain reaction (qPCR) and Western blot. The expression of miR-206 was detected by qPCR. Dual luciferase assay was detected to confirm the specific binding sites of miR-206 and Cx43. RESULTS: (1) The proliferation activity of 206m-group cell (0.74 ± 0.16) was significantly lower than that of control group (1.12 ± 0.23) (t = -3.066, P = 0.037) while that of 206i-group cell (1.43 ± 0.26) was higher than that of control group (0.98 ± 0.14) (t = 3.635, P = 0.022). (2) Transwell tests showed the migration and invasion of 206m-group cell decreased significantly (migration0.56 ± 0.01 vs 0.63 ± 0.01, t = -23.00, P = 0.002; invasion0.79 ± 0.01 vs 0.99 ± 0.01, t = -21.200, P = 0.002), but that of 206i-group cell increased significantly (migration0.97 ± 0.11 vs 0.61 ± 0.09, t = 32.787, P = 0.001; invasion1.10 ± 0.01 vs 0.93 ± 0.05, t = 5.167, P = 0.035). (3) The expressions of MMP-2,MMP-9 and Cx43 decreased and the expression of BRMS-1 increased in 206m-group cell and vice versa in 206i group. (4) The expression of miR-206 in lymph node-negative group of clinical breast cancer sample was higher than that of lymph node-positive one. And there was statistical difference (Z = -2.098, P = 0.003). And the expression of Cx43 was opposite. (5) Dual luciferase reporter assay confirmed the specific binding sites of hsa-miR-206 and Cx43. CONCLUSION: Hsa-miR-206 has negative controls of proliferation, migration and invasion of breast cancer cell by targeting Cx43.