title: Loss of miR-204 expression enhances glioma migration and stem cell-like phenotype.
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.
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ying
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Jueheng
authors.initials: J
authors.lastname: Wu
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Han
authors.initials: H
authors.lastname: Tian
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: Shi-Yuan
authors.initials: SY
authors.lastname: Cheng
authors.forename: Mengfeng
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D019175:DNA Methylation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000473:pathology*; D058953:Neural Stem Cells / Q000473:pathology; D010641:Phenotype; D014183:Transplantation, Heterologous
chemical_list: C549404:MIRN204 microRNA, human; D035683:MicroRNAs