Open AccessmiR-135b Contributes to the Radioresistance by Targeting GSK3β in Human Glioblastoma Multiforme Cells
Author(s) -
Shifu Xiao,
Zhen Yang,
Ruiyan Lv,
Jia Zhao,
Ming Wu,
Yixiang Liao,
Qing Liu
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0108810
Subject(s) - radioresistance , gene knockdown , cancer research , radiosensitivity , downregulation and upregulation , microrna , cell culture , biology , gsk3b , gsk 3 , medicine , radiation therapy , kinase , microbiology and biotechnology , genetics , gene
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 GSK3β (Glycogen synthase kinase 3 beta) was a novel direct target of miR-135b. Moreover, GSK3β protein expression was downregulated in U87R cells and restored expression of GSK3β increased radiosensitivity of U87R cells. In addition, clinical data indicated that the expression of miR-135b or GSK3β 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-GSK3β axis may be a novel candidate for developing rational therapeutic strategies for human GBM treatment.