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Neuro Oncol. 2017 Jan;19(1):55-65. doi: 10.1093/neuonc/now129. Epub 2016 Jul 28.

miR-423-5p contributes to a malignant phenotype and temozolomide chemoresistance in glioblastomas.

Author information

1
Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China (S.L.); Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China (A.Z., Q.H., W.Y., Y.Y.); Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (Y.L.).

Abstract

BACKGROUND:

Gliomas are based on a genetic abnormality and present with a dismal prognosis. MicroRNAs (miRNAs) are considered to be important mediators of gene expression in glioma tissues.

METHODS:

Real-time PCR was used to analyze the expression of microRNA-423-5p (miR-423-5p) in human glioma samples and normal brain tissue. Apoptosis, cell cycle, proliferation, immunostaining, transwell, in vitro 2D and 3D migration, and chemosensitivity assays were performed to assess the phenotypic changes in glioma cells overexpressing miRNA-423-5p. Western blotting was used to determine the expression of inhibitor of growth 4 (ING-4)in glioma tissues, and a luciferase reporter assay was conducted to confirm whether ING-4 is a direct target of miR-423-5p. Western blotting was used to identify the potential signaling pathways that are affected in glioma cell growth by miR-423-5p. Xenograft tumors were examined in vivo for the carcinogenic effects of miR-423-5p in glioma tissues.

RESULTS:

We first reported that miR-423-5p expression was increased in gliomas and was a potential tumor promoter via targeting ING-4. The overexpression of miR-423-5p resulted in upregulation of important signaling molecules such as p-AKT and p-ERK1/2. In clinical samples, miR-423-5p was dysregulated, and a corresponding alteration in ING-4 expression was observed (P = .0207). Furthermore, the overexpression of miR-423-5p strengthened glioma cell proliferation, angiogenesis, and invasion. Finally, miR-423-5p overexpression also strengthened GBM neurosphere formation and rendered glioma cells resistant to temozolomide (TMZ).

CONCLUSION:

This study establishes that miR-423-5p functions as an oncogene in glioma tissues by suppressing ING-4 and suggests that it has therapeutic potential for glioma.

KEYWORDS:

ING-4; chemoresistance; glioma; miR-423-5p

PMID:
27471108
PMCID:
PMC5193021
DOI:
10.1093/neuonc/now129
[Indexed for MEDLINE]
Free PMC Article

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