2. Academic Validation
  3. EGFRvIII epigenetically regulates ARHI to promote glioma cell proliferation and migration

EGFRvIII epigenetically regulates ARHI to promote glioma cell proliferation and migration

  • Exp Mol Pathol. 2020 Feb;112:104344. doi: 10.1016/j.yexmp.2019.104344.
Yan Zheng 1,  Yuan Ma 2,  Han Yue 3,  Guangzhi Liu 3,  Shuangyin Han 4
Affiliations

Affiliations

  • 1 Key Laboratory of Immunization of Kidney Disease, People's Hospital of Henan Province, Zhengzhou University, China.
  • 2 Institute of Clinical Medicine, Universities of Henan Province, The First Affiliated Hospital of Zhengzhou University, China.
  • 3 Stem Cell Research Center, People's Hospital of Henan Province, Zhengzhou University, China.
  • 4 Key Laboratory of Immunization of Kidney Disease, People's Hospital of Henan Province, Zhengzhou University, China. Electronic address: [email protected].
PMID: 31751560 DOI: 10.1016/j.yexmp.2019.104344
Abstract

Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation widely expressed in glioma. However, its role and molecular mechanism in glioma have not been completely elucidated. Immunohistochemistry analyses of EGFRvIII, enhancer of zeste homolog 2 (EZH2) and aplysia Ras homolog I (ARHI) were performed in tumor tissues from patients with glioma. Regulatory mechanisms among EGFRvIII, EZH2 and ARHI were examined by western blot and chromatin immunoprecipitation (ChIP). Cell proliferation and migration of glioma cells were examined. EGFRvIII and EZH2 expression were upregulated, while ARHI was downregulated in glioma tissues. EZH2 knockdown increased ARHI expression in glioma cell lines. ChIP assay suggested that EZH2 was enriched in the ARHI promoter. Furthermore, ectopic expression of EGFRvIII upregulated EZH2, suppressed ARHI expression, and promoted glioma cell proliferation. Additionally, treatment with 3-deazaneplanocin A (DZNep, an inhibitor of EZH2) inhibited expression of EZH2, increased protein level of ARHI, and partially abrogated the promoting effects of ARHI knockdown on glioma cell proliferation and migration. In summary, EGFRvIII-mediated epigenetic suppression of ARHI promoted glioma cell proliferation and migration via upregulating EZH2.

Keywords

ARHI; EGFRvIII; EZH2; Glioma.

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