Radiation induces autophagy via histone h4 lysine 20 trimethylation in non-small cell lung cancer cells

Tae Gul Lee, Seo Yun Kim, Hye Ryoun Kim, Hyunggee Kim, Cheol Hyeon Kim

Research output: Contribution to journalArticle

Abstract

Background/Aim: Radiotherapy-induced autophagy affects radiation-sensitivity and radiotherapy efficacy. Histone modifications also occur during radiotherapy. This study assessed radiotherapy effects on histone modification and autophagy in non-small cell lung cancer (NSCLC) cells. Materials and Methods: NSCLC cells were subjected to γ- irradiation. Autophagy was detected using western blotting and acridine orange staining. Radiation effect on cell growth was evaluated by clonogenic assay. Histone modifications were assessed by western blotting. Next generation sequencings (NGSs) were conducted to identify histone modification target genes. Results: Radio-protective autophagy and histone H4 lysine 20 trimethylation (H4K20me3) were up-regulated after irradiation. By NGSs, genes that are differentially expressed upon irradiation were identified, including the candidate H4K20me3 target gene GABARAPL1. Furthermore, we showed that GABARAPL1 is essential for the radiationinduced autophagy. Conclusion: Our findings revealed the regulatory axis of radiation-induced H4K20me3-GABARAPL1 in radio-protective autophagy. Modulation of this axis may be a new strategy to enhance radiotherapy efficacy in NSCLC.

Original languageEnglish
Pages (from-to)2537-2548
Number of pages12
JournalAnticancer research
Volume40
Issue number5
DOIs
Publication statusPublished - 2020 May

Keywords

  • Autophagy
  • GABARAPL1
  • Histone modification
  • Non-small cell lung cancer
  • Radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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