MiR-223/PAX6 Axis Regulates Glioblastoma Stem Cell Proliferation and the Chemo Resistance to TMZ via Regulating PI3K/Akt Pathway

J Cell Biochem. 2017 Oct;118(10):3452-3461. doi: 10.1002/jcb.26003. Epub 2017 Jun 6.

Abstract

Chemotherapy is a standard strategy for glioma, while chemoresistance remains a major therapeutic challenge in current clinical practice. Our present study was aimed to determine whether inhibition of the miR-223/paired box 6 (PAX6) pathway could increase the sensitivity of glioma to Temozolomide. An elevated level of miR-223 was observed in glioma tissues. Exogenous miR-223 promoted cell survival when exposed to Temozolomide (TMZ), while miR-223 inhibition could reverse this process. The RNA and protein levels of PAX6 were significantly decreased by exogenous miR-223, and the 3'-untranslated region of PAX6 was shown to be a target of miR-223. Besides, it has also been reported that PI3K/Akt signaling pathway is pivotal to regulate glioma growth and proliferation. In the present study, we revealed that miR-223/PAX6 axis regulated the growth, invasion, and chemo resistance of glioblastoma stem cells to TMZ via regulating PI3K/Akt signaling pathway, which present a novel potential therapy for intervention of glioblastoma. Taken together, our findings shed new light on the miR-223/PAX6 pathway in glioma and this pathway might modulate the sensitivity of glioma to TMZ via regulating PI3K/Akt signaling pathway. J. Cell. Biochem. 118: 3452-3461, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: CHEMORESISTANCE; GLIOMA; PAIRED BOX 6 (PAX6); TEMOZOLOMIDE (TMZ); miR-223.

MeSH terms

  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Cell Proliferation
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / pharmacology
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • PAX6 Transcription Factor / genetics
  • PAX6 Transcription Factor / metabolism*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Temozolomide

Substances

  • MIRN223 microRNA, human
  • MicroRNAs
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • RNA, Neoplasm
  • Dacarbazine
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Temozolomide