Loss of miR-204 expression enhances glioma migration and stem cell-like phenotype

Zhe Ying, Yun Li, Jueheng Wu, Xun Zhu, Yi Yang, Han Tian, Wei Li, Bo Hu, Shi Yuan Cheng, Mengfeng Li*

*Corresponding author for this work

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

Phenotypic similarities have long been recognized between subpopulations of glioma and neural stem cells. Many of these similar properties, including the robust abilities to self-renew, migrate, and invade, are hallmarks of glioma cells that render them extremely aggressive. However, the molecular mechanisms underlying this character, particularly in glioma stem-like cells that drive this disease, remain poorly understood. Here, we report the results of a differential miRNA expression screen that compared glioma and neural stem cells, where we found that miR-204 was markedly downregulated in both types of cells. Mechanistic investigations revealed that miR-204 simultaneously suppressed self-renewal, stem cell-associated phenotype, and migration of glioma cells by targeting the stemness-governing transcriptional factor SOX4 and the migration-promoting receptor EphB2. Restoring miR-204 expression in glioma cells suppressed tumorigenesis and invasiveness in vivo and increased overall host survival. Further evaluation revealed that the miR-204 promoter was hypermethylated and that attenuating promoter methylation was sufficient to upregulate miR-204 in glioma cells. Together, our findings reveal miR-204 as a pivotal regulator of the development of stem cell-like phenotypes and cell motility in malignant glioma cells.

Original languageEnglish (US)
Pages (from-to)990-999
Number of pages10
JournalCancer Research
Volume73
Issue number2
DOIs
StatePublished - Jan 15 2013

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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