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

doi:10.21873/anticanres.14224

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 journal › Article › peer-review

8 Citations (Scopus)

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 language	English
Pages (from-to)	2537-2548
Number of pages	12
Journal	Anticancer research
Volume	40
Issue number	5
DOIs	https://doi.org/10.21873/anticanres.14224
Publication status	Published - 2020 May

Keywords

Autophagy
GABARAPL1
Histone modification
Non-small cell lung cancer
Radiotherapy

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.21873/anticanres.14224

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

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.",

keywords = "Autophagy, GABARAPL1, Histone modification, Non-small cell lung cancer, Radiotherapy",

author = "Lee, {Tae Gul} and Kim, {Seo Yun} and Kim, {Hye Ryoun} and Hyunggee Kim and Kim, {Cheol Hyeon}",

note = "Funding Information: This study was supported by a grant from the Korea Institute of Radiological and Medical Sciences (KIRAMS), funded by Ministry of Science and ICT (MSIT), Republic of Korea (50550-2020). Publisher Copyright: {\textcopyright} 2020 International Institute of Anticancer Research. All rights reserved.",

year = "2020",

month = may,

doi = "10.21873/anticanres.14224",

language = "English",

volume = "40",

pages = "2537--2548",

journal = "Anticancer research",

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publisher = "International Institute of Anticancer Research",

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T1 - Radiation induces autophagy via histone h4 lysine 20 trimethylation in non-small cell lung cancer cells

AU - Lee, Tae Gul

AU - Kim, Seo Yun

AU - Kim, Hye Ryoun

AU - Kim, Hyunggee

AU - Kim, Cheol Hyeon

N1 - Funding Information: This study was supported by a grant from the Korea Institute of Radiological and Medical Sciences (KIRAMS), funded by Ministry of Science and ICT (MSIT), Republic of Korea (50550-2020). Publisher Copyright: © 2020 International Institute of Anticancer Research. All rights reserved.

PY - 2020/5

Y1 - 2020/5

N2 - 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.

AB - 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.

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KW - Histone modification

KW - Non-small cell lung cancer

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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