APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma
Mammalian apurinic/apyrimidinic endonuclease 1 (APE1, APEX1) is a multifunctional enzyme that maintains cellular homeostasis. It is involved in the base excision repair (BER) pathway and plays a key role in radiation-induced DNA damage response. However, the relationship between APE1-driven radiatio...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523323001353 |
| _version_ | 1797745974832005120 |
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| author | Jing Zhou Zixin Wei Chuan Yang Dexin Jia Bo Pan Yuan Zeng Di Sun Yan Yu |
| author_facet | Jing Zhou Zixin Wei Chuan Yang Dexin Jia Bo Pan Yuan Zeng Di Sun Yan Yu |
| author_sort | Jing Zhou |
| collection | DOAJ |
| description | Mammalian apurinic/apyrimidinic endonuclease 1 (APE1, APEX1) is a multifunctional enzyme that maintains cellular homeostasis. It is involved in the base excision repair (BER) pathway and plays a key role in radiation-induced DNA damage response. However, the relationship between APE1-driven radiation resistance and pyroptosis in lung adenocarcinoma (LUAD) cells and the underlying molecular mechanisms remain unclear. We found that APE1 was significantly upregulated in LUAD tissues compared to para-carcinoma tissues and promoted the proliferation and invasion of LUAD cells in vitro and in vivo. Mechanistically, APE1 inhibited pyroptosis by inactivating the interferon gene stimulator (STING) pathway via direct interaction with AIM2 and DDX41, as detected by RNA-seq and co-immunoprecipitation. APE1 protects LUAD cells against radiation-induced damage and induces radio-resistance by targeting the STING pathway. It can induce pyroptosis and is negatively regulated by interactions with AIM2 and DDX41. Therefore, APE1 inhibitors should be considered to enhance the radiosensitivity of LUAD cells and improve patient prognosis and therapeutic outcomes. Thus, APE1 play a role in the tumor immune microenvironment and in tumor immunotherapy. |
| first_indexed | 2024-03-12T15:31:26Z |
| format | Article |
| id | doaj.art-67f7646368cc47ce87d61bd4b9338b48 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-03-12T15:31:26Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-67f7646368cc47ce87d61bd4b9338b482023-08-10T04:34:08ZengElsevierTranslational Oncology1936-52332023-10-0136101749APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinomaJing Zhou0Zixin Wei1Chuan Yang2Dexin Jia3Bo Pan4Yuan Zeng5Di Sun6Yan Yu7Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin 150040, ChinaDepartment of Medical Oncology, Sichuan Cancer Hospital, Chengdu 610042, ChinaDepartment of Gastroenterology, Heilongjiang Provincial Hospital, Harbin 150001, ChinaDepartment of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Nangang District, Harbin 150040, ChinaDepartment of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Nangang District, Harbin 150040, ChinaDepartment of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Nangang District, Harbin 150040, ChinaDepartment of Radiotherapy Technology Center, Harbin Medical University Cancer Hospital, Harbin 150040, ChinaDepartment of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Nangang District, Harbin 150040, China; Corresponding author.Mammalian apurinic/apyrimidinic endonuclease 1 (APE1, APEX1) is a multifunctional enzyme that maintains cellular homeostasis. It is involved in the base excision repair (BER) pathway and plays a key role in radiation-induced DNA damage response. However, the relationship between APE1-driven radiation resistance and pyroptosis in lung adenocarcinoma (LUAD) cells and the underlying molecular mechanisms remain unclear. We found that APE1 was significantly upregulated in LUAD tissues compared to para-carcinoma tissues and promoted the proliferation and invasion of LUAD cells in vitro and in vivo. Mechanistically, APE1 inhibited pyroptosis by inactivating the interferon gene stimulator (STING) pathway via direct interaction with AIM2 and DDX41, as detected by RNA-seq and co-immunoprecipitation. APE1 protects LUAD cells against radiation-induced damage and induces radio-resistance by targeting the STING pathway. It can induce pyroptosis and is negatively regulated by interactions with AIM2 and DDX41. Therefore, APE1 inhibitors should be considered to enhance the radiosensitivity of LUAD cells and improve patient prognosis and therapeutic outcomes. Thus, APE1 play a role in the tumor immune microenvironment and in tumor immunotherapy.http://www.sciencedirect.com/science/article/pii/S1936523323001353RadiosensitivityLUADAPE1STINGPyroptosis |
| spellingShingle | Jing Zhou Zixin Wei Chuan Yang Dexin Jia Bo Pan Yuan Zeng Di Sun Yan Yu APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma Translational Oncology Radiosensitivity LUAD APE1 STING Pyroptosis |
| title | APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma |
| title_full | APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma |
| title_fullStr | APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma |
| title_full_unstemmed | APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma |
| title_short | APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma |
| title_sort | ape1 promotes radiation resistance against radiation induced pyroptosis by inhibiting the sting pathway in lung adenocarcinoma |
| topic | Radiosensitivity LUAD APE1 STING Pyroptosis |
| url | http://www.sciencedirect.com/science/article/pii/S1936523323001353 |
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