The nociceptin receptor promotes autophagy through NF-kB signaling and is transcriptionally regulated by E2F1 in HCC
Abstract Opioids and their receptors are involved in cancer progression. However, the roles of the nociceptin receptor (NOP) and its antagonist (JTC801) in hepatocellular carcinoma (HCC) are poorly understood. The prognostic value of NOP expression was evaluated using tissue microarray and immunohis...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-04-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-022-00978-7 |
| _version_ | 1819022358405447680 |
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| author | Xiaoshuang Zhou Dongtai Chen Yan Yan Qiang Li Wei Xing Yanling Liu Yonghua Chen Dongyin Wang Yunfei Yuan Jingdun Xie Weian Zeng Jiahao Pan |
| author_facet | Xiaoshuang Zhou Dongtai Chen Yan Yan Qiang Li Wei Xing Yanling Liu Yonghua Chen Dongyin Wang Yunfei Yuan Jingdun Xie Weian Zeng Jiahao Pan |
| author_sort | Xiaoshuang Zhou |
| collection | DOAJ |
| description | Abstract Opioids and their receptors are involved in cancer progression. However, the roles of the nociceptin receptor (NOP) and its antagonist (JTC801) in hepatocellular carcinoma (HCC) are poorly understood. The prognostic value of NOP expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human HCC cohort. The biological role and mechanism of NOP in HCC tumor growth were determined in vitro and in vivo. We found that NOP was associated with the clinicopathological features and survival outcomes of HCC patients. NOP overexpression promoted HCC growth in vitro and in vivo. Mechanistically, NOP activated NF-kB signaling to promote autophagy, which inhibited apoptosis, in HCC cells. An inhibitor of autophagy, 3-MA, and an inhibitor of NF-kB, JSH-23, attenuated the function of NOP in HCC. E2F1 was identified as a transcription factor of NOP. The oncogenic role of NOP was positively regulated by E2F1. Furthermore, JTC801, a selective antagonist of NOP, abolished the function of NOP by inhibiting NF-kB signaling and autophagy. Our study demonstrates that NOP is an oncogene in HCC. We provide a potential therapeutic candidate and prognostic predictor for HCC. JTC801 could become a potential drug for HCC therapy. |
| first_indexed | 2024-12-21T04:21:44Z |
| format | Article |
| id | doaj.art-1672995b8cae4e378d0f5f33d762a9c6 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-12-21T04:21:44Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-1672995b8cae4e378d0f5f33d762a9c62022-12-21T19:16:08ZengNature Publishing GroupCell Death Discovery2058-77162022-04-018111310.1038/s41420-022-00978-7The nociceptin receptor promotes autophagy through NF-kB signaling and is transcriptionally regulated by E2F1 in HCCXiaoshuang Zhou0Dongtai Chen1Yan Yan2Qiang Li3Wei Xing4Yanling Liu5Yonghua Chen6Dongyin Wang7Yunfei Yuan8Jingdun Xie9Weian Zeng10Jiahao Pan11Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineDepartment of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineDepartment of Anesthesiology, Huizhou Municipal Central HospitalDepartment of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineDepartment of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineDepartment of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineDepartment of Anesthesiology, Peking University Shenzhen HospitalDepartment of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineDepartment of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineDepartment of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineDepartment of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineDepartment of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineAbstract Opioids and their receptors are involved in cancer progression. However, the roles of the nociceptin receptor (NOP) and its antagonist (JTC801) in hepatocellular carcinoma (HCC) are poorly understood. The prognostic value of NOP expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human HCC cohort. The biological role and mechanism of NOP in HCC tumor growth were determined in vitro and in vivo. We found that NOP was associated with the clinicopathological features and survival outcomes of HCC patients. NOP overexpression promoted HCC growth in vitro and in vivo. Mechanistically, NOP activated NF-kB signaling to promote autophagy, which inhibited apoptosis, in HCC cells. An inhibitor of autophagy, 3-MA, and an inhibitor of NF-kB, JSH-23, attenuated the function of NOP in HCC. E2F1 was identified as a transcription factor of NOP. The oncogenic role of NOP was positively regulated by E2F1. Furthermore, JTC801, a selective antagonist of NOP, abolished the function of NOP by inhibiting NF-kB signaling and autophagy. Our study demonstrates that NOP is an oncogene in HCC. We provide a potential therapeutic candidate and prognostic predictor for HCC. JTC801 could become a potential drug for HCC therapy.https://doi.org/10.1038/s41420-022-00978-7 |
| spellingShingle | Xiaoshuang Zhou Dongtai Chen Yan Yan Qiang Li Wei Xing Yanling Liu Yonghua Chen Dongyin Wang Yunfei Yuan Jingdun Xie Weian Zeng Jiahao Pan The nociceptin receptor promotes autophagy through NF-kB signaling and is transcriptionally regulated by E2F1 in HCC Cell Death Discovery |
| title | The nociceptin receptor promotes autophagy through NF-kB signaling and is transcriptionally regulated by E2F1 in HCC |
| title_full | The nociceptin receptor promotes autophagy through NF-kB signaling and is transcriptionally regulated by E2F1 in HCC |
| title_fullStr | The nociceptin receptor promotes autophagy through NF-kB signaling and is transcriptionally regulated by E2F1 in HCC |
| title_full_unstemmed | The nociceptin receptor promotes autophagy through NF-kB signaling and is transcriptionally regulated by E2F1 in HCC |
| title_short | The nociceptin receptor promotes autophagy through NF-kB signaling and is transcriptionally regulated by E2F1 in HCC |
| title_sort | nociceptin receptor promotes autophagy through nf kb signaling and is transcriptionally regulated by e2f1 in hcc |
| url | https://doi.org/10.1038/s41420-022-00978-7 |
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