ACT001 inhibited CD133 transcription by targeting and inducing Olig2 ubiquitination degradation
Abstract Lung cancer is the most lethal malignancies with high aggressive and poor prognosis. Until now, the five-year survival rate has not been improved which brings serious challenge to human health. Lung cancer stem cells (LCSCs) serve as the root of cancer occurrence, progression, recurrence, a...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-03-01
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| Series: | Oncogenesis |
| Online Access: | https://doi.org/10.1038/s41389-023-00462-6 |
| _version_ | 1827974269604200448 |
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| author | Huiting Deng Hailin Liu Guoyue Yang Dandan Wang Ying Luo Chenglong Li Zhenchang Qi Zhili Liu Peng Wang Yanfang Jia Yingtang Gao Yahui Ding |
| author_facet | Huiting Deng Hailin Liu Guoyue Yang Dandan Wang Ying Luo Chenglong Li Zhenchang Qi Zhili Liu Peng Wang Yanfang Jia Yingtang Gao Yahui Ding |
| author_sort | Huiting Deng |
| collection | DOAJ |
| description | Abstract Lung cancer is the most lethal malignancies with high aggressive and poor prognosis. Until now, the five-year survival rate has not been improved which brings serious challenge to human health. Lung cancer stem cells (LCSCs) serve as the root of cancer occurrence, progression, recurrence, and drug resistance. Therefore, effective anti-cancer agents and molecular mechanisms which could specifically eliminate LCSCs are urgently needed for drug design. In this article, we discovered Olig2 was overexpressed in clinical lung cancer tissues and acted as a transcription factor to regulate cancer stemness by regulating CD133 gene transcription. The results suggested Olig2 could be a promising target in anti-LCSCs therapy and new drugs targeted Olig2 may exhibit excellent clinical results. Furthermore, we verified ACT001, a guaianolide sesquiterpene lactone in phase II clinical trial with excellent glioma remission, inhibited cancer stemness by directly binding to Olig2 protein, inducing Olig2 ubiquitination degradation and inhibiting CD133 gene transcription. All these results suggested that Olig2 could be an excellent druggable target in anti-LCSCs therapy and lay a foundation for the further application of ACT001 in the treatment of lung cancer in clinical. |
| first_indexed | 2024-04-09T19:51:38Z |
| format | Article |
| id | doaj.art-287f918620fd4c0da7d4964d52943a71 |
| institution | Directory Open Access Journal |
| issn | 2157-9024 |
| language | English |
| last_indexed | 2024-04-09T19:51:38Z |
| publishDate | 2023-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Oncogenesis |
| spelling | doaj.art-287f918620fd4c0da7d4964d52943a712023-04-03T05:41:11ZengNature Publishing GroupOncogenesis2157-90242023-03-0112111210.1038/s41389-023-00462-6ACT001 inhibited CD133 transcription by targeting and inducing Olig2 ubiquitination degradationHuiting Deng0Hailin Liu1Guoyue Yang2Dandan Wang3Ying Luo4Chenglong Li5Zhenchang Qi6Zhili Liu7Peng Wang8Yanfang Jia9Yingtang Gao10Yahui Ding11Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin Third Central Hospital affiliated to Nankai University, Nankai UniversityDepartment of Lung Cancer, Tianjin Medical University Cancer Institute and HospitalTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin Third Central Hospital affiliated to Nankai University, Nankai UniversityTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin Third Central Hospital affiliated to Nankai University, Nankai UniversityTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin Third Central Hospital affiliated to Nankai University, Nankai UniversityTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin Third Central Hospital affiliated to Nankai University, Nankai UniversityTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin Third Central Hospital affiliated to Nankai University, Nankai UniversityTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin Third Central Hospital affiliated to Nankai University, Nankai UniversityTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin Third Central Hospital affiliated to Nankai University, Nankai UniversityTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin Third Central Hospital affiliated to Nankai University, Nankai UniversityTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin Third Central Hospital affiliated to Nankai University, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, College of Chemistry, Nankai University, Haihe Education ParkAbstract Lung cancer is the most lethal malignancies with high aggressive and poor prognosis. Until now, the five-year survival rate has not been improved which brings serious challenge to human health. Lung cancer stem cells (LCSCs) serve as the root of cancer occurrence, progression, recurrence, and drug resistance. Therefore, effective anti-cancer agents and molecular mechanisms which could specifically eliminate LCSCs are urgently needed for drug design. In this article, we discovered Olig2 was overexpressed in clinical lung cancer tissues and acted as a transcription factor to regulate cancer stemness by regulating CD133 gene transcription. The results suggested Olig2 could be a promising target in anti-LCSCs therapy and new drugs targeted Olig2 may exhibit excellent clinical results. Furthermore, we verified ACT001, a guaianolide sesquiterpene lactone in phase II clinical trial with excellent glioma remission, inhibited cancer stemness by directly binding to Olig2 protein, inducing Olig2 ubiquitination degradation and inhibiting CD133 gene transcription. All these results suggested that Olig2 could be an excellent druggable target in anti-LCSCs therapy and lay a foundation for the further application of ACT001 in the treatment of lung cancer in clinical.https://doi.org/10.1038/s41389-023-00462-6 |
| spellingShingle | Huiting Deng Hailin Liu Guoyue Yang Dandan Wang Ying Luo Chenglong Li Zhenchang Qi Zhili Liu Peng Wang Yanfang Jia Yingtang Gao Yahui Ding ACT001 inhibited CD133 transcription by targeting and inducing Olig2 ubiquitination degradation Oncogenesis |
| title | ACT001 inhibited CD133 transcription by targeting and inducing Olig2 ubiquitination degradation |
| title_full | ACT001 inhibited CD133 transcription by targeting and inducing Olig2 ubiquitination degradation |
| title_fullStr | ACT001 inhibited CD133 transcription by targeting and inducing Olig2 ubiquitination degradation |
| title_full_unstemmed | ACT001 inhibited CD133 transcription by targeting and inducing Olig2 ubiquitination degradation |
| title_short | ACT001 inhibited CD133 transcription by targeting and inducing Olig2 ubiquitination degradation |
| title_sort | act001 inhibited cd133 transcription by targeting and inducing olig2 ubiquitination degradation |
| url | https://doi.org/10.1038/s41389-023-00462-6 |
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