Abnormal expression of menin predicts the pathogenesis and poor prognosis of adult gliomas

Cancer Gene Ther. 2020 Aug;27(7-8):539-547. doi: 10.1038/s41417-019-0127-5. Epub 2019 Aug 6.

Abstract

Several brain tumors is closely related to the disorder of chromatin histone modification, whereas the epigenetic mechanisms of the incidence of highly malignant adult glioma is not yet deeply studied. Deletion or mutation of the MEN1 gene, which encodes the epigenetic regulator menin, specifically induces poorly differentiated neuroendocrine tumors; however, the biological and clinical importance of MEN1 in the nervous system remains poorly understood. Menin expression was robustly activated in 44.4% of adult gliomas. Abnormally high expression of menin was closely related to a shorter median survival time of 20 months, a larger tumor volume and a higher percentage of Ki67 staining. Interestingly, menin expression was also activated in the cytoplasm of tumor cells (38.8%) and was also closely related to the poor prognosis of patients with glioma. Importantly, in a screening of 96 types of small-molecule targeted histone modification regulators, menin inhibitors were found to significantly block the proliferation of adult glioma cells. Our findings confirm that menin is a potential biomarker of poor prognosis in adult gliomas, independent of the WHO grade. Targeting menin may effectively inhibit certain gliomas, and this information provides novel insight into therapeutic strategies for glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioma / diagnosis
  • Glioma / genetics*
  • Glioma / metabolism
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Young Adult

Substances

  • MEN1 protein, human
  • Proto-Oncogene Proteins