Biomedicine & Pharmacotherapy (Feb 2022)

EZH2 as a new therapeutic target in brain tumors: Molecular landscape, therapeutic targeting and future prospects

  • Mahshid Deldar Abad Paskeh,
  • Atefeh Mehrabi,
  • Mohammad Hossein Gholami,
  • Amirhossein Zabolian,
  • Ehsan Ranjbar,
  • Hossein Saleki,
  • Adnan Ranjbar,
  • Mehrdad Hashemi,
  • Yavuz Nuri Ertas,
  • Kiavash Hushmandi,
  • Sepideh Mirzaei,
  • Milad Ashrafizadeh,
  • Ali Zarrabi,
  • Saeed Samarghandian

Journal volume & issue
Vol. 146
p. 112532

Abstract

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Brain tumors are responsible for high mortality and morbidity worldwide. The brain tumor treatment depends on identification of molecular pathways involved in progression and malignancy. Enhancer of zeste homolog 2 (EZH2) has obtained much attention in recent years in field of cancer therapy due to its aberrant expression and capacity in modulating expression of genes by binding to their promoter and affecting methylation status. The present review focuses on EZH2 signaling in brain tumors including glioma, glioblastoma, astrocytoma, ependymomas, medulloblastoma and brain rhabdoid tumors. EZH2 signaling mainly participates in increasing proliferation and invasion of cancer cells. However, in medulloblastoma, EZH2 demonstrates tumor-suppressor activity. Furthermore, EZH2 can regulate response of brain tumors to chemotherapy and radiotherapy. Various molecular pathways can function as upstream mediators of EZH2 in brain tumors including lncRNAs and miRNAs. Owing to its enzymatic activity, EZH2 can bind to promoter of target genes to induce methylation and affects their expression. EZH2 can be considered as an independent prognostic factor in brain tumors that its upregulation provides undesirable prognosis. Both anti-tumor agents and gene therapies such as siRNA have been developed for targeting EZH2 in cancer therapy.

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