USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway
Abstract Ubiquitin-specific protease 3 (USP3) plays an important role in the progression of various tumors. However, the role of USP3 in osteosarcoma (OS) remains poorly understood. The aim of this study was to explore the biological function of USP3 in OS and the underlying molecular mechanism. We...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2024-03-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-024-06624-7 |
| _version_ | 1797233228380110848 |
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| author | Anan Li Shijiang Wang Jiangbo Nie Shining Xiao Xinsheng Xie Yu Zhang Weilai Tong Geliang Yao Ning Liu Fan Dan Zhiguo Shu Jiaming Liu Zhili Liu Feng Yang |
| author_facet | Anan Li Shijiang Wang Jiangbo Nie Shining Xiao Xinsheng Xie Yu Zhang Weilai Tong Geliang Yao Ning Liu Fan Dan Zhiguo Shu Jiaming Liu Zhili Liu Feng Yang |
| author_sort | Anan Li |
| collection | DOAJ |
| description | Abstract Ubiquitin-specific protease 3 (USP3) plays an important role in the progression of various tumors. However, the role of USP3 in osteosarcoma (OS) remains poorly understood. The aim of this study was to explore the biological function of USP3 in OS and the underlying molecular mechanism. We found that OS had higher USP3 expression compared with that of normal bone tissue, and high expression of USP3 was associated with poor prognosis in patients with OS. Overexpression of USP3 significantly increased OS cell proliferation, migration, and invasion. Mechanistically, USP3 led to the activation of the PI3K/AKT signaling pathway in OS by binding to EPHA2 and then reducing its protein degradation. Notably, the truncation mutant USP3-F2 (159–520) interacted with EPHA2, and amino acid 203 was found to play an important role in this process. And knockdown of EPHA2 expression reversed the pro-tumour effects of USP3-upregulating. Thus, our study indicates the USP3/EPHA2 axis may be a novel potential target for OS treatment. |
| first_indexed | 2024-04-24T16:12:50Z |
| format | Article |
| id | doaj.art-0c0efc77bab74c9bad86f8459b463001 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-24T16:12:50Z |
| publishDate | 2024-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-0c0efc77bab74c9bad86f8459b4630012024-03-31T11:37:02ZengNature Publishing GroupCell Death and Disease2041-48892024-03-0115311210.1038/s41419-024-06624-7USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathwayAnan Li0Shijiang Wang1Jiangbo Nie2Shining Xiao3Xinsheng Xie4Yu Zhang5Weilai Tong6Geliang Yao7Ning Liu8Fan Dan9Zhiguo Shu10Jiaming Liu11Zhili Liu12Feng Yang13Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityOrthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityOrthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityOrthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityMedical Innovation Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityOrthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityOrthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityOrthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityOrthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityOrthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityOrthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityOrthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityOrthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityOrthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityAbstract Ubiquitin-specific protease 3 (USP3) plays an important role in the progression of various tumors. However, the role of USP3 in osteosarcoma (OS) remains poorly understood. The aim of this study was to explore the biological function of USP3 in OS and the underlying molecular mechanism. We found that OS had higher USP3 expression compared with that of normal bone tissue, and high expression of USP3 was associated with poor prognosis in patients with OS. Overexpression of USP3 significantly increased OS cell proliferation, migration, and invasion. Mechanistically, USP3 led to the activation of the PI3K/AKT signaling pathway in OS by binding to EPHA2 and then reducing its protein degradation. Notably, the truncation mutant USP3-F2 (159–520) interacted with EPHA2, and amino acid 203 was found to play an important role in this process. And knockdown of EPHA2 expression reversed the pro-tumour effects of USP3-upregulating. Thus, our study indicates the USP3/EPHA2 axis may be a novel potential target for OS treatment.https://doi.org/10.1038/s41419-024-06624-7 |
| spellingShingle | Anan Li Shijiang Wang Jiangbo Nie Shining Xiao Xinsheng Xie Yu Zhang Weilai Tong Geliang Yao Ning Liu Fan Dan Zhiguo Shu Jiaming Liu Zhili Liu Feng Yang USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway Cell Death and Disease |
| title | USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway |
| title_full | USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway |
| title_fullStr | USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway |
| title_full_unstemmed | USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway |
| title_short | USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway |
| title_sort | usp3 promotes osteosarcoma progression via deubiquitinating epha2 and activating the pi3k akt signaling pathway |
| url | https://doi.org/10.1038/s41419-024-06624-7 |
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