MiR-135b contributes to the radioresistance by targeting GSK3? in human glioblastoma multiforme cells.

ABSTRACT: Radioresistance remains a major challenge in the treatment of glioblastoma multiforme (GBM). Recent data strongly suggests the important role of miRNAs in cancer progression and therapeutic response. Here, we have established a radioresistant human GBM cell line U87R derived from parental U87 and found miR-135b expression was upregulated in U87R cells. miR-135b knockdown reversed radioresistance of U87R cells, and miR-135b overexpression enhanced radioresistance of U87 cells. Mechanically, bioinformatics analysis combined with experimental analysis demonstrated GSK3? (Glycogen synthase kinase 3 beta) was a novel direct target of miR-135b. Moreover, GSK3? protein expression was downregulated in U87R cells and restored expression of GSK3? increased radiosensitivity of U87R cells. In addition, clinical data indicated that the expression of miR-135b or GSK3? was significantly association with IR resistance of GBM samples. Our findings suggest miR-135b is involved in the radioresistance of human GBM cells and miR-135b-GSK3? axis may be a novel candidate for developing rational therapeutic strategies for human GBM treatment.

SUBMITTER: Xiao S 

PROVIDER: S-EPMC4181861 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature