4.5 Article

A lentivirus-mediated miR-23b sponge diminishes the malignant phenotype of glioma cells in vitro and in vivo

期刊

ONCOLOGY REPORTS
卷 31, 期 4, 页码 1573-1580

出版社

SPANDIDOS PUBL LTD
DOI: 10.3892/or.2014.3012

关键词

glioblastoma; microRNA sponge; microRNA-23b; malignant phenotype

类别

资金

  1. National High Technology Research and Development Program 863 [2012AA02A508]
  2. China National Natural Scientific Foundation [81001128, 81172406, 81372703]
  3. Research Fund for the Doctoral Program of Higher Education of China [20111202110004]
  4. Natural Science Foundation of Tianjin Municipal Science and Technology Commission [12JCZDJC24300]
  5. Tianjin City High School Science & Technology Fund [2009CD01, 20090228]

向作者/读者索取更多资源

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.

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