MiR-200c and miR-141 inhibit ZEB1 synergistically and suppress glioma cell growth and migration.

OBJECTIVE This study aimed to investigate the expression of miR-200c and miR-141 in glioma tissues and cell lines and then to study their regulative effect on ZEB1 expression and on glioma cell growth and migration. MATERIALS AND METHODS QRT-PCR analysis was performed to detect miR-200c and miR-141 expression in 10 paired glioma tissues and adjacent normal tissues from patients with glioblastoma multiforme (GBM) and in glioma cell lines. U87 and U251 cells were transfected with miR-200c mimics, miR-141 mimics or ZEB1 siRNA respectively. ZEB1 expression was detected qRT-PCR and Western blot assay. MTT assay, flow cytometry and wound healing assay were performed to examine the tumor suppressive effects of the miR-200c/miR-141-ZEB1 axis on glioma cells. RESULTS Both miR-200c and miR-141 were significantly lower in glioma tissues than in adjacent normal tissues. The glioma cell lines, including U87, U251 and A172 also had significantly decreased miR-200c and miR-141 expression than normal tissues. ZEB1 expression had at least two-fold increase in glioma tissues than in normal tissues. Both miR-200c and miR-141 could significantly induce ZEB1 mRNA degradation and suppress ZEB1 protein expression. ZEB1 siRNA presented similar growth and migration inhibiting and apoptosis inducing effect to miR-200c and miR-141 mimics in U87 cells. CONCLUSIONS MiR-200c and miR-141 are significantly downregulated in glioma tissues and cell lines and can significantly induce ZEB1 mRNA degradation and suppress ZEB1 protein expression in the cells. ZEB1 is a functional downstream target of miR-200c and miR-141 in inhibiting glioma cell growth and migration.