Gliomas display a microRNA expression profile reminiscent of neural precursor cells

Iris Lavon*, Daniel Zrihan, Avital Granit, Ofira Einstein, Nina Fainstein, Malkiel A. Cohen, Mikhal A. Cohen, Bracha Zelikovitch, Yigal Shoshan, Sergei Spektor, Benjamin E. Reubinoff, Yakov Felig, Offer Gerlitz, Tamir Ben-Hur, Yohav Smith, Tali Siegal

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

Gliomas express many genes that play a role in neural precursor cells (NPCs), but no direct comparison between glioma and stem cell (SC) gene expression profiles has been performed. To investigate the similarities and differences between gliomas and SCs, we compared the microRNA (miRNA) expression signatures of glial tumors, embryonic SCs (ESCs), NPCs, and normal adult brains from both human and mouse tissues. We demonstrated that both human gliomas (regardless of their grade) and methylcholanthrene-induced mouse glioma shared an miRNA expression profile that is reminiscent of NPCs. About half of the miRNAs expressed in the shared profile clustered in seven genomic regions susceptible to genetic/epigenetic alterations in various cancers. These clusters comprised the miR17 family, mir183-182, and the SC-specific clusters mir367-302 and mir371-373, which are upregulated in gliomas, ESCs, and NPCs. The bipartite cluster of 7146 miRNAs on chromosome 14q32.31, which might represent the largest tumor suppressor miRNA cluster, was downregulated in the shared expression profile. This study provides the first evidence for association between these clusters and gliomas. Despite the broad similarity in the miRNA expression profiles, 15 miRNAs showed disparate expression between SC and gliomas. Ten miRNAs belong to the 2 SC-specific clusters and the remaining (mir135b, mir141, mir205, mir200C, and mir301a) have been previously shown to associate with malignancies. Our finding showed that all gliomas displayed NPC-like miRNA signatures, which may have implications for studies of glioma origins. Furthermore, careful study of the 15 miRNAs that differ in expression between SCs and gliomas, particularly those 5 that are not SC-specific, may enhance our understanding of gliomagenesis.

Original languageAmerican English
Pages (from-to)422-433
Number of pages12
JournalNeuro-Oncology
Volume12
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

Keywords

  • Gliomas
  • MicroRNA
  • Neural precursor cells
  • Stem cells

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