MicroRNA-34a promotes cell cycle arrest and apoptosis and suppresses cell adhesion by targeting DUSP1 in osteosarcoma

Abstract

MicroRNAs are often deregulated in most cancer types and have important functions in carcinogenesis and cancer progression. Here, we studied the function of microRNA-34 (miR-34a) in osteosarcoma MG63 and U-2OS cells by expressed with pre-miR-34a, anti-miR-34a and corresponding negative controls, respectively. Cells proliferation, cell cycle and apoptosis was measured by MTT and flow cytometry assay. The effect of miR-34a on DUSP1 expression was evaluated by luciferase assays, real-time PCR and western blot assay. The data showed that miR-34a reduced the proliferation of MG63 cells through prompting cell cycle arrest at G0/G1 phase, cell apoptosis, and suppressed cell adhesion ability. Whereas anti-miR-34a increases U-2OS cell proliferation by preventing cell apoptosis, and promotes cell adhesion. Finally, we identified Dual-specificity phosphatase 1 (DUSP1) as the target gene of miR-34a in osteosarcoma cells and confirmed that DUSP1 enhanced the proliferation through inhibiting cell cycle arrest at G0/G1 phase and apoptosis, and inhibits the decreased cell adhesion induced by miR-34a. However, inhibition of DUSP1 resulted in substantially decreased proliferation and adhesion, and cell cycle arrest in G0/G1 phase and cell apoptosis similar to that observed with miR-34a in U-2OS cells. Our findings find out an important function of miR-34a as a novel tumor-suppressor in osteosarcoma pathogenesis through inhibition of DUSP1.