miR-128 and miR-149 enhance the chemosensitivity of temozolomide by Rap1B-mediated cytoskeletal remodeling in glioblastoma
miR-128 and miR-149 enhance the chemosensitivity of temozolomide by Rap1B-mediated cytoskeletal remodeling in glioblastoma
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DOI：
10.3892/or.2014.3318
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发表时间：
2014-09-01
期刊：
影响因子：
4.2
通讯作者：
Li, Guiyuan
中科院分区：
文献类型：
--
作者：
She, Xiaoling;Yu, Zhibin;Li, Guiyuan
多形性胶质母细胞瘤（GBM）是影响人类的最致命的疾病之一，其特点往往是生存率低，对化疗和放疗具有高耐药性。替莫唑胺（TMZ）是一种口服烷基化剂，广泛用于GBM术后的治疗。虽然TMZ可以抑制GBM的生长，但TMZ耐药也很常见，并导致许多治疗失败的病例。研究表明，miRNA的异常表达与GBM的标志性恶性特性有关。因此，基于mirna的抗癌治疗方法已经被开发出来，无论是单独使用还是与标准靶向治疗联合使用，以提高化疗药物的疗效。在本研究中，我们证明了miR-128和miR-149在胶质母细胞瘤中表达下调，它们的过表达通过靶向rap1b介导的细胞骨架和相关分子改变来抑制胶质母细胞瘤细胞的侵袭。此外，miR-128和miR-149增强了胶质母细胞瘤细胞对TMZ的化学敏感性。
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.