DNMT-dependent suppression of microRNA regulates the induction of GBM tumor-propagating phenotype by Oct4 and Sox2

H. Lopez-Bertoni, B. Lal, A. Li, M. Caplan, Hugo Guerrero Cazares, C. G. Eberhart, Alfredo Quinones-Hinojosa, M. Glas, B. Scheffler, J. Laterra, Y. Li

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Cancer stem-like cells represent poorly differentiated multipotent tumor-propagating cells that contribute disproportionately to therapeutic resistance and tumor recurrence. Transcriptional mechanisms that control the phenotypic conversion of tumor cells lacking tumor-propagating potential to tumor-propagating stem-like cells remain obscure. Here we show that the reprogramming transcription factors Oct4 and Sox2 induce glioblastoma cells to become stem-like and tumor-propagating via a mechanism involving direct DNA methyl transferase (DNMT) promoter transactivation, resulting in global DNA methylation- and DNMT-dependent downregulation of multiple microRNAs (miRNAs). We show that one such downregulated miRNA, miRNA-148a, inhibits glioblastoma cell stem-like properties and tumor-propagating potential. This study identifies a novel and targetable molecular circuit by which glioma cell stemness and tumor-propagating capacity are regulated.

Original languageEnglish (US)
Pages (from-to)3994-4004
Number of pages11
JournalOncogene
Volume34
Issue number30
DOIs
StatePublished - Jul 23 2015
Externally publishedYes

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Transferases
MicroRNAs
Phenotype
DNA
Neoplasms
Glioblastoma
Stem Cells
Down-Regulation
Neoplastic Stem Cells
DNA Methylation
Glioma
Transcriptional Activation
Transcription Factors
Recurrence

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics
  • Medicine(all)

Cite this

DNMT-dependent suppression of microRNA regulates the induction of GBM tumor-propagating phenotype by Oct4 and Sox2. / Lopez-Bertoni, H.; Lal, B.; Li, A.; Caplan, M.; Guerrero Cazares, Hugo; Eberhart, C. G.; Quinones-Hinojosa, Alfredo; Glas, M.; Scheffler, B.; Laterra, J.; Li, Y.

In: Oncogene, Vol. 34, No. 30, 23.07.2015, p. 3994-4004.

Research output: Contribution to journalArticle

Lopez-Bertoni, H, Lal, B, Li, A, Caplan, M, Guerrero Cazares, H, Eberhart, CG, Quinones-Hinojosa, A, Glas, M, Scheffler, B, Laterra, J & Li, Y 2015, 'DNMT-dependent suppression of microRNA regulates the induction of GBM tumor-propagating phenotype by Oct4 and Sox2', Oncogene, vol. 34, no. 30, pp. 3994-4004. https://doi.org/10.1038/onc.2014.334
Lopez-Bertoni, H. ; Lal, B. ; Li, A. ; Caplan, M. ; Guerrero Cazares, Hugo ; Eberhart, C. G. ; Quinones-Hinojosa, Alfredo ; Glas, M. ; Scheffler, B. ; Laterra, J. ; Li, Y. / DNMT-dependent suppression of microRNA regulates the induction of GBM tumor-propagating phenotype by Oct4 and Sox2. In: Oncogene. 2015 ; Vol. 34, No. 30. pp. 3994-4004.
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