A lentivirus-mediated miR-23b sponge diminishes the malignant phenotype of glioma cells in vitro and in vivo
A lentivirus-mediated miR-23b sponge diminishes the malignant phenotype of glioma cells in vitro and in vivo
复制标题
慢病毒介导的 miR-23b 海绵在体外和体内减少神经胶质瘤细胞的恶性表型
DOI：
10.3892/or.2014.3012
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发表时间：
2014-04-01
期刊：
影响因子：
4.2
通讯作者：
Han, Lei
中科院分区：
文献类型：
--
作者：
Chen, Luyue;Zhang, Kailiang;Han, Lei
microRNA（miRNA）海绵是具有重复的miRNA结合序列的RNA分子，其可以将miRNA与其内源性靶mRNA隔离，并且稳定表达的miRNA海绵对于体外和体内的长期功能丧失研究特别有价值。多形性胶质母细胞瘤（GBM）是成人中最常见的原发性脑肿瘤，其特征在于异常的血管生成、侵袭和迁移能力，这些标志性特征使得该疾病不可治愈。尽管如此，在过去的几十年里，临床治疗的改善和对潜在分子机制的更好理解已经实现。miR-23 b以前被发现在GBM中作为肿瘤癌基因发挥作用。在本研究中，我们采用了一种microRNA海绵，使用慢病毒载体强制表达，在体外和体内敲低miR-23 b的表达，并评估了对胶质瘤血管生成，侵袭和迁移的多效性效应。我们证明了在胶质瘤细胞系和原位肿瘤小鼠模型中抑制miR-23 b通过下调HIF-1 α、β-连环蛋白、MMP 2、MMP 9、VEGF和ZEB 1以及增加VHL和E-cadherin的表达而导致肿瘤恶性程度降低。因此，我们建议这种miR-23 b海绵可以单独或与目前的靶向治疗联合开发成为一种有前景的抗癌疗法。
microRNA (miRNA) sponges are RNA molecules with repeated miRNA binding sequences that can sequester miRNAs from their endogenous target mRNAs, and a stably expressed miRNA sponge is particularly valuable for long-term loss-of-function studies in vitro and in vivo. Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and is characterized by extraordinarily angiogenic, invasive and migratory capabilities, hallmark features that make the disease incurable. Nonetheless, improvements in clinical treatment and a better understanding of the underlying molecular mechanisms have been achieved within the past few decades. miR-23b has previously been found to function as a tumor oncogene in GBM. In the present study, we employed an microRNA sponge that was forcibly expressed using a lentiviral vector to knock down the expression of miR-23b in vitro and in vivo and assessed the pleiotropic effects on glioma angiogenesis, invasion and migration. We demonstrated that the inhibition of miR-23b in glioma cell lines and orthotopic tumor mouse models resulted in a reduction in tumor malignancy, through the downregulation of HIF-1 alpha, beta-catenin, MMP2, MMP9, VEGF and ZEB1 and increased expression of VHL and E-cadherin. Therefore, we suggest that this miR-23b sponge could be developed into a promising anticancer therapy either alone or in combination with current targeted therapies.