Ribosomal protein L5 induces cellular senescence via p53-p21-pRb pathway to mediate relapse of acute myeloid leukemia
Abstract Cellular senescence plays a critical role in the relapse of acute myeloid leukemia (AML), yet the underlying mechanisms remain incompletely understood. Here, we investigated the function of ribosomal protein L5 (RPL5) in mediating cellular senescence and its impact on AML relapse. In relaps...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-12108-1 |
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| author | Wanqiu Zhang Linlin Liu Ruotong Chen Haotian Yan Qing Zhang Xiyang Ren Huiping Wang Yi Dong Wanying Xue Zhimin Zhai Qianshan Tao |
| author_facet | Wanqiu Zhang Linlin Liu Ruotong Chen Haotian Yan Qing Zhang Xiyang Ren Huiping Wang Yi Dong Wanying Xue Zhimin Zhai Qianshan Tao |
| author_sort | Wanqiu Zhang |
| collection | DOAJ |
| description | Abstract Cellular senescence plays a critical role in the relapse of acute myeloid leukemia (AML), yet the underlying mechanisms remain incompletely understood. Here, we investigated the function of ribosomal protein L5 (RPL5) in mediating cellular senescence and its impact on AML relapse. In relapsed AML patients, the proportion of senescent cells and the expression of RPL5 were elevated, compared to patients at newly diagnosised or in complete remission, suggesting a potential link between RPL5 and AML relapse. Following chemotherapy induction, a cellular senescence model was constructed using KG-1 A cells, with RPL5 expression significantly elevated. Knockdown of RPL5 suppressed cellular senescence and enhanced apoptosis, possibly due to different regulatory mechanisms for cell proliferation and senescence. Moreover, downregulation of RPL5 mitigated chemotherapy-induced senescence and improved the response of AML cells to chemotherapy drug. Mechanistically, RPL5 regulated cellular senescence via the p53-p21-pRb pathway and its downregulation led to a reduction in senescence-related protein expression levels. These findings suggest that RPL5 plays a critical role in mediating cellular senescence and chemotherapy response in AML, providing insights into novel therapeutic strategies for overcoming chemotherapy resistance and preventing disease relapse. Future studies may explore RPL5-targeted therapies and assess their clinical applicability in AML. |
| format | Article |
| id | doaj-art-1e7e9e2e02014155b2dc9b4f70e94d6f |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-1e7e9e2e02014155b2dc9b4f70e94d6f2025-08-20T03:42:35ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-12108-1Ribosomal protein L5 induces cellular senescence via p53-p21-pRb pathway to mediate relapse of acute myeloid leukemiaWanqiu Zhang0Linlin Liu1Ruotong Chen2Haotian Yan3Qing Zhang4Xiyang Ren5Huiping Wang6Yi Dong7Wanying Xue8Zhimin Zhai9Qianshan Tao10Department of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Intensive Care Unit, Fuyang Hospital of Anhui Medical UniversityDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityAbstract Cellular senescence plays a critical role in the relapse of acute myeloid leukemia (AML), yet the underlying mechanisms remain incompletely understood. Here, we investigated the function of ribosomal protein L5 (RPL5) in mediating cellular senescence and its impact on AML relapse. In relapsed AML patients, the proportion of senescent cells and the expression of RPL5 were elevated, compared to patients at newly diagnosised or in complete remission, suggesting a potential link between RPL5 and AML relapse. Following chemotherapy induction, a cellular senescence model was constructed using KG-1 A cells, with RPL5 expression significantly elevated. Knockdown of RPL5 suppressed cellular senescence and enhanced apoptosis, possibly due to different regulatory mechanisms for cell proliferation and senescence. Moreover, downregulation of RPL5 mitigated chemotherapy-induced senescence and improved the response of AML cells to chemotherapy drug. Mechanistically, RPL5 regulated cellular senescence via the p53-p21-pRb pathway and its downregulation led to a reduction in senescence-related protein expression levels. These findings suggest that RPL5 plays a critical role in mediating cellular senescence and chemotherapy response in AML, providing insights into novel therapeutic strategies for overcoming chemotherapy resistance and preventing disease relapse. Future studies may explore RPL5-targeted therapies and assess their clinical applicability in AML.https://doi.org/10.1038/s41598-025-12108-1Acute myeloid leukemiaRelapseCellular senescenceRibosome stressRibosomal protein L5 |
| spellingShingle | Wanqiu Zhang Linlin Liu Ruotong Chen Haotian Yan Qing Zhang Xiyang Ren Huiping Wang Yi Dong Wanying Xue Zhimin Zhai Qianshan Tao Ribosomal protein L5 induces cellular senescence via p53-p21-pRb pathway to mediate relapse of acute myeloid leukemia Scientific Reports Acute myeloid leukemia Relapse Cellular senescence Ribosome stress Ribosomal protein L5 |
| title | Ribosomal protein L5 induces cellular senescence via p53-p21-pRb pathway to mediate relapse of acute myeloid leukemia |
| title_full | Ribosomal protein L5 induces cellular senescence via p53-p21-pRb pathway to mediate relapse of acute myeloid leukemia |
| title_fullStr | Ribosomal protein L5 induces cellular senescence via p53-p21-pRb pathway to mediate relapse of acute myeloid leukemia |
| title_full_unstemmed | Ribosomal protein L5 induces cellular senescence via p53-p21-pRb pathway to mediate relapse of acute myeloid leukemia |
| title_short | Ribosomal protein L5 induces cellular senescence via p53-p21-pRb pathway to mediate relapse of acute myeloid leukemia |
| title_sort | ribosomal protein l5 induces cellular senescence via p53 p21 prb pathway to mediate relapse of acute myeloid leukemia |
| topic | Acute myeloid leukemia Relapse Cellular senescence Ribosome stress Ribosomal protein L5 |
| url | https://doi.org/10.1038/s41598-025-12108-1 |
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