miR-484/MAP2/c-Myc-positive regulatory loop in glioma promotes tumor-initiating properties through ERK1/2 signaling

J Mol Histol. 2018 Apr;49(2):209-218. doi: 10.1007/s10735-018-9760-9. Epub 2018 Feb 26.

Abstract

Glioma is the most common intracranial malignant tumor. Cancer stem cells (CSCs) are resistant to chemotherapy and radiotherapy, and are closely related to cancer metastasis and recurrence. In this study, we aimed to explore the effect of miR-484 on glioma stemness and the underlying mechanism involved. miR-484 enhanced glioma tumor-initiating properties in vitro and in vivo. Moreover, miR-484 was shown to directly target MAP2, resulting in activation of ERK1/2 signaling and promotion of stemness in glioma. The ERK1/2 signaling facilitated the formation of a miR-484/MAP2/c-Myc positive feedback loop in glioma. High miR-484 expression predicted a poor prognosis for glioma patients, and high MAP2 expression predicted a good prognosis for glioma patients. Low miR-484 expression and high MAP2 expression was associated with the best prognosis in glioma. Our study suggests that miR-484 and MAP2 can be utilized as predictors for the clinical diagnosis and prognosis of glioma, and miR-484 and MAP2 are potential targets for the treatment of glioma.

Keywords: Glioma; MAP2; MicroRNAs; Stemness; c-Myc; miR-484.

MeSH terms

  • Cell Transformation, Neoplastic / metabolism
  • Feedback, Physiological
  • Glioma / diagnosis
  • Glioma / metabolism*
  • Humans
  • MAP Kinase Signaling System*
  • MicroRNAs / metabolism*
  • Microtubule-Associated Proteins / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-myc / metabolism
  • Signal Transduction
  • Tumor Cells, Cultured

Substances

  • MAP2 protein, human
  • MIRN484 microRNA, human
  • MYC protein, human
  • MicroRNAs
  • Microtubule-Associated Proteins
  • Proto-Oncogene Proteins c-myc