Downregulation of miR-452 promotes stem-like traits and tumorigenicity of gliomas.

Abstract

PURPOSE:

miR-452 is reported to be required for neural crest stem cell differentiation during neural crest development. However, the biologic role of miR-452 in gliomas remains unclear. The aim of the present study was to evaluate the effect of miR-452 on the stem-like properties and tumorigenesis of glioma cells.

EXPERIMENTAL DESIGN:

The expression of miR-452 was examined in glioma cells and glioma tissues using real-time PCR. The effects of miR-452 on stem-like traits and tumorigenesis were investigated in vitro and in vivo using patient-derived glioma cells and glioma cell lines. Western blotting and luciferase reporter assays were conducted to examine the negative regulation of Bmi-1, LEF1, and TCF4 by miR-452. The methylation of the miR-452 promoter region was examined by bisulfite genomic sequencing PCR.

RESULTS:

miR-452 was markedly downregulated in glioma cells and clinical glioma tissues. miR-452 levels were inversely correlated with World Health Organization (WHO) grades and patient survival. miR-452 directly targeted and suppressed multiple stemness regulators, including Bmi-1, LEF1, and TCF4, resulting in reduced stem-like traits and tumorigenesis of glioma cells in vitro and in vivo. Furthermore, we showed that downregulation of miR-452 in gliomas was caused by hypermethylation of its promoter region.

CONCLUSIONS:

Downregulation of miR-452 plays an important role in promoting the stem-like traits and tumorigenesis of gliomas and may represent a novel prognostic biomarker and therapeutic target for the disease.

• Authors: Liping Liu, Kun Chen, Jueheng Wu, Ling Shi, Bo Hu, Shiyuan Cheng, Mengfeng Li, Libing Song
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 19 Issue 13 Pg. 3429-38 (Jul 01 2013) ISSN: 1557-3265 [Electronic] United States
• PMID: 23695168 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2013 AACR.

Chemical References

• MIRN452 microRNA, human
• MicroRNAs

Topics

• Cell Line, Tumor
• Cell Transformation, Neoplastic (genetics)
• DNA Methylation
• Down-Regulation
• Gene Expression Regulation, Neoplastic
• Glioma (genetics, metabolism, mortality)
• Humans
• MicroRNAs (genetics)
• Neoplastic Stem Cells (metabolism)
• Prognosis
• Promoter Regions, Genetic
• Quantitative Trait, Heritable