title: miR-135b contributes to the radioresistance by targeting GSK3β 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 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.
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guanzhou, Guangdong, People's Republic of China.
authors.forename: Songhua
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guanzhou, Guangdong, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guanzhou, Guangdong, People's Republic of China.
authors.forename: Ruiyan
authors.initials: R
authors.lastname: Lv
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guanzhou, Guangdong, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South university, Changsha, Hunan, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South university, Changsha, Hunan, People's Republic of China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South university, Changsha, Hunan, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011836:Radiation Tolerance / Q000235:genetics* / Q000528:radiation effects; D011839:Radiation, Ionizing
chemical_list: C544965:MIRN135 microRNA, human; D035683:MicroRNAs; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3