Ribosomal protein L9 is a potential therapeutic target for B-ALL through the activation of the p53 signaling pathway
B-cell acute lymphocytic leukemia (B-ALL) is a malignant hematological disorder marked by the aberrant proliferation of abnormal B lymphocytes. Although recent advancements have highlighted the pivotal role of ribosomes in the progression of B-ALL, the specific function of ribosomal protein L9 (RPL9...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1560706/full |
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| author | Xinxin Li Xinxin Li Wenting Meng Xi Wang Siyong Huang Jianbin Wang Han Liang Dailing Si |
| author_facet | Xinxin Li Xinxin Li Wenting Meng Xi Wang Siyong Huang Jianbin Wang Han Liang Dailing Si |
| author_sort | Xinxin Li |
| collection | DOAJ |
| description | B-cell acute lymphocytic leukemia (B-ALL) is a malignant hematological disorder marked by the aberrant proliferation of abnormal B lymphocytes. Although recent advancements have highlighted the pivotal role of ribosomes in the progression of B-ALL, the specific function of ribosomal protein L9 (RPL9), a key component of ribosomal structural protein, still unclear. In this study, we observed a significant upregulation of RPL9 in human B-ALL cells compared to normal B cells, suggesting RPL9’s potential key role in B-ALL progression. Enforced RPL9 knockdown (KD) led to decreased proliferation and increased apoptosis in B-ALL cells compared to the control group. Furthermore, RPL9 KD significantly extended the survival time of NCG mice bearing B-ALL cells in vivo compared to controls. Mechanistically, our findings indicate that RPL9 KD triggers nucleolar stress, disrupts ribosome biosynthesis, and activates the p53 signaling pathway. Building upon our recent investigation into the positive regulatory influence of FTO on m6A-modified RPL9, we discovered that FTO overexpression can mitigate the activation of p53 signaling induced by RPL9 KD. Our findings further suggest that RPL9 KD increases MICA/B mRNA and protein expression in B-ALL cells, which serves as crucial ligands of NK cell’s NKG2D, potentially heightening their sensitivity to NK cell-mediated cytotoxicity. In summary, our study suggests that RPL9 KD suppresses B-ALL proliferation and upregulates immunotherapy targets, highlighting the important role of RPL9 as a potential target for conventional and immunotherapy of B-ALL. |
| format | Article |
| id | doaj-art-f8f33c9c3dcb48ddaa86b4d89ee62d53 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-f8f33c9c3dcb48ddaa86b4d89ee62d532025-08-20T02:49:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15607061560706Ribosomal protein L9 is a potential therapeutic target for B-ALL through the activation of the p53 signaling pathwayXinxin Li0Xinxin Li1Wenting Meng2Xi Wang3Siyong Huang4Jianbin Wang5Han Liang6Dailing Si7Xi’an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi’an, ChinaResearch & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, ChinaDepartment of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaDepartment of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaDepartment of Hematology, Xi’an International Medical Center Hospital, Xi’an, ChinaDepartment of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an, ChinaAnalysis & Testing Laboratory for Life Sciences and Medicine, Fourth Military Medical University, Xi’an, ChinaAnalysis & Testing Laboratory for Life Sciences and Medicine, Fourth Military Medical University, Xi’an, ChinaB-cell acute lymphocytic leukemia (B-ALL) is a malignant hematological disorder marked by the aberrant proliferation of abnormal B lymphocytes. Although recent advancements have highlighted the pivotal role of ribosomes in the progression of B-ALL, the specific function of ribosomal protein L9 (RPL9), a key component of ribosomal structural protein, still unclear. In this study, we observed a significant upregulation of RPL9 in human B-ALL cells compared to normal B cells, suggesting RPL9’s potential key role in B-ALL progression. Enforced RPL9 knockdown (KD) led to decreased proliferation and increased apoptosis in B-ALL cells compared to the control group. Furthermore, RPL9 KD significantly extended the survival time of NCG mice bearing B-ALL cells in vivo compared to controls. Mechanistically, our findings indicate that RPL9 KD triggers nucleolar stress, disrupts ribosome biosynthesis, and activates the p53 signaling pathway. Building upon our recent investigation into the positive regulatory influence of FTO on m6A-modified RPL9, we discovered that FTO overexpression can mitigate the activation of p53 signaling induced by RPL9 KD. Our findings further suggest that RPL9 KD increases MICA/B mRNA and protein expression in B-ALL cells, which serves as crucial ligands of NK cell’s NKG2D, potentially heightening their sensitivity to NK cell-mediated cytotoxicity. In summary, our study suggests that RPL9 KD suppresses B-ALL proliferation and upregulates immunotherapy targets, highlighting the important role of RPL9 as a potential target for conventional and immunotherapy of B-ALL.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1560706/fullB-ALLRPL9cell proliferationapoptosisp53 signaling pathway |
| spellingShingle | Xinxin Li Xinxin Li Wenting Meng Xi Wang Siyong Huang Jianbin Wang Han Liang Dailing Si Ribosomal protein L9 is a potential therapeutic target for B-ALL through the activation of the p53 signaling pathway Frontiers in Immunology B-ALL RPL9 cell proliferation apoptosis p53 signaling pathway |
| title | Ribosomal protein L9 is a potential therapeutic target for B-ALL through the activation of the p53 signaling pathway |
| title_full | Ribosomal protein L9 is a potential therapeutic target for B-ALL through the activation of the p53 signaling pathway |
| title_fullStr | Ribosomal protein L9 is a potential therapeutic target for B-ALL through the activation of the p53 signaling pathway |
| title_full_unstemmed | Ribosomal protein L9 is a potential therapeutic target for B-ALL through the activation of the p53 signaling pathway |
| title_short | Ribosomal protein L9 is a potential therapeutic target for B-ALL through the activation of the p53 signaling pathway |
| title_sort | ribosomal protein l9 is a potential therapeutic target for b all through the activation of the p53 signaling pathway |
| topic | B-ALL RPL9 cell proliferation apoptosis p53 signaling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1560706/full |
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