title: miR-128 and miR-149 enhance the chemosensitivity of temozolomide by Rap1B-mediated cytoskeletal remodeling in glioblastoma.
abstract: Glioblastoma multiforme (GBM) is one of the most deadly diseases affecting humans, and is often characterized by poor survival and by high resistance to chemotherapy and radiotherapy. Temozolomide (TMZ) is an oral alkylating agent which is widely used in the treatment of GBM following surgery. Although TMZ may restrain GBM growth, TMZ resistance is also common and accounts for numerous cases of treatment failure. Studies indicate that aberrant miRNA expression is associated with hallmark malignant properties of GBM. Thus, miRNA-based anticancer therapeutic approaches have been exploited, either alone or in combination with standard targeted therapies to enhance the efficacy of chemotherapy agents. In the present study, we demonstrated that the expression of miR-128 and miR-149 was downregulated in glioblastoma, and their overexpression inhibited the invasion of glioblastoma cells by targeting Rap1B-mediated cytoskeletal and related molecular alterations. Moreover, miR-128 and miR-149 enhanced the chemosensitivity of glioblastoma cells to TMZ.
authors.affiliation: Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: She
authors.affiliation: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Lei
authors.affiliation: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Zeyou
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Wu
authors.affiliation: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D000077204:Temozolomide; D015854:Up-Regulation; D020668:rap GTP-Binding Proteins / Q000235:genetics*
chemical_list: D018906:Antineoplastic Agents, Alkylating; C545189:MIRN128 microRNA, human; C551557:MIRN149 microRNA, human; D035683:MicroRNAs; D003606:Dacarbazine; C116753:RAP1B protein, human; D020668:rap GTP-Binding Proteins; D000077204:Temozolomide