DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathway
Osteosarcoma (OS) is a primary malignant tumor of the bone characterized by poor prognosis due to chemotherapy resistance and high recurrence rates. DJ-1 (PARK7) is known as an oncogene and its abnormal expression is related to the poor prognosis of various types of malignant tumors. It was found in...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1036401/full |
| _version_ | 1811244639183699968 |
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| author | Zhitao Han Lining Wang Lining Wang Dongshuo Wang Luosheng Zhang Yifeng Bi Xinlei Zheng Weibo Liu Guangjian Bai Zhenhua Wang Wei Wan Yong Ma Xiaopan Cai Tielong Liu Qi Jia |
| author_facet | Zhitao Han Lining Wang Lining Wang Dongshuo Wang Luosheng Zhang Yifeng Bi Xinlei Zheng Weibo Liu Guangjian Bai Zhenhua Wang Wei Wan Yong Ma Xiaopan Cai Tielong Liu Qi Jia |
| author_sort | Zhitao Han |
| collection | DOAJ |
| description | Osteosarcoma (OS) is a primary malignant tumor of the bone characterized by poor prognosis due to chemotherapy resistance and high recurrence rates. DJ-1 (PARK7) is known as an oncogene and its abnormal expression is related to the poor prognosis of various types of malignant tumors. It was found in this study that upregulated expression of DJ-1 was closely correlated with the prognosis of OS patients by promoting the proliferation, migration and chemotherapy resistance of OS cells in vitro through regulating the activity of CDK4 but not through the oxidation mechanism or AKT pathway. The combination of DJ-1 and CDK4 promoted RB phosphorylation, leading to the dissociation of E2F1 into the nucleus to regulate the expression of cell cycle-related genes. The tumor xenograft mouse model demonstrated that DJ-1 knockout suppressed tumor growth in vivo. All these findings indicate that DJ-1 can affect the occurrence and progression of OS by regulating the CDK/RB/E2F1axis, suggesting a novel therapeutic opportunity for OS patients. |
| first_indexed | 2024-04-12T14:28:40Z |
| format | Article |
| id | doaj.art-6be2a4bc6df24791b42fa7980a5ef7c7 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T14:28:40Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-6be2a4bc6df24791b42fa7980a5ef7c72022-12-22T03:29:22ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.10364011036401DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathwayZhitao Han0Lining Wang1Lining Wang2Dongshuo Wang3Luosheng Zhang4Yifeng Bi5Xinlei Zheng6Weibo Liu7Guangjian Bai8Zhenhua Wang9Wei Wan10Yong Ma11Xiaopan Cai12Tielong Liu13Qi Jia14School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaSchool of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaLaboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaSchool of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaDepartment of Orthopedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaDepartment of Orthopedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaSchool of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaDepartment of Orthopaedics, the Fourth Medical Centre, Chinese PLA General Hospital, Beijing, ChinaDepartment of Orthopedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaDepartment of Laboratory Medicine, Changzheng Hospital, Naval Medical University, Shanghai, ChinaDepartment of Orthopedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaSchool of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaDepartment of Orthopedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaDepartment of Orthopedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaDepartment of Orthopedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaOsteosarcoma (OS) is a primary malignant tumor of the bone characterized by poor prognosis due to chemotherapy resistance and high recurrence rates. DJ-1 (PARK7) is known as an oncogene and its abnormal expression is related to the poor prognosis of various types of malignant tumors. It was found in this study that upregulated expression of DJ-1 was closely correlated with the prognosis of OS patients by promoting the proliferation, migration and chemotherapy resistance of OS cells in vitro through regulating the activity of CDK4 but not through the oxidation mechanism or AKT pathway. The combination of DJ-1 and CDK4 promoted RB phosphorylation, leading to the dissociation of E2F1 into the nucleus to regulate the expression of cell cycle-related genes. The tumor xenograft mouse model demonstrated that DJ-1 knockout suppressed tumor growth in vivo. All these findings indicate that DJ-1 can affect the occurrence and progression of OS by regulating the CDK/RB/E2F1axis, suggesting a novel therapeutic opportunity for OS patients.https://www.frontiersin.org/articles/10.3389/fonc.2022.1036401/fullDJ-1 (PARK7)cdk4RBE2F1osteosarcoma (OS)target therapy |
| spellingShingle | Zhitao Han Lining Wang Lining Wang Dongshuo Wang Luosheng Zhang Yifeng Bi Xinlei Zheng Weibo Liu Guangjian Bai Zhenhua Wang Wei Wan Yong Ma Xiaopan Cai Tielong Liu Qi Jia DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathway Frontiers in Oncology DJ-1 (PARK7) cdk4 RB E2F1 osteosarcoma (OS) target therapy |
| title | DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathway |
| title_full | DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathway |
| title_fullStr | DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathway |
| title_full_unstemmed | DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathway |
| title_short | DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathway |
| title_sort | dj 1 promotes osteosarcoma progression through activating cdk4 rb e2f1 signaling pathway |
| topic | DJ-1 (PARK7) cdk4 RB E2F1 osteosarcoma (OS) target therapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1036401/full |
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