MicroRNA-223 enhances radiation sensitivity of U87MG cells in vitro and in vivo by targeting ataxia telangiectasia mutated.

摘要: Purpose Ataxia telangiectasia mutated (ATM) protein is important in the DNA damage response because it repairs radiation-induced cancers. We examined effect of microRNA-223 (miR-223), a regulator ATM expression, on radiation sensitivity cancer cells. Methods and Materials Human embryonic kidney 293 T (293T) cells were infected with pLL3.7-miR-223 plasmid to generate -empty virus (EV) lentivirus (miR-223 EV). A dual luciferase assay which reporter contained wild-type 3′ untranslated region (UTR) was performed. U87MG cells miR-223 or EV establish overexpressed stable cell lines (U87-223 U87-EV, respectively). Cells irradiated in vitro, dose enhancement ratios at 2 Gy (DER 2 ) calculated. Hind legs BALB/c athymic mice injected U87-223 U87-EV cells; after 2 weeks, half tumors irradiated. Tumor volumes tracked for total 5 weeks. Results The showed significant reduction activity 293T cotransfected 3′UTR compared that control. Overexpression expression significantly downregulated U87-223 cells (ATM/β-actin mRNA 1.0 vs 1.5, P  = 1.32, 3 1.7 cm ). However, irradiation decreased tumor size miR-223-expressing those controls (0.033 cm 0.829 cm Conclusions overexpression downregulates sensitizes U87 cells in vitro in vivo. MicroRNA-223 may be novel cancer-targeting therapy, although its cancer- patient-specific roles are currently undefined.