RBM15-dependent m6A modification mediates progression of non-small cell lung cancer cells
Abstract Background Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer, contributing significantly to global health and economic challenges. This study elucidated the role of RBM15 in NSCLC progression through its involvement in m6A modifications. Methods RBM15 levels in NSCLC...
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BMC
2024-12-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-024-01018-z |
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| author | Man Wang Yujiao Qin Xiaoqi Ai Xiuhua Liu |
| author_facet | Man Wang Yujiao Qin Xiaoqi Ai Xiuhua Liu |
| author_sort | Man Wang |
| collection | DOAJ |
| description | Abstract Background Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer, contributing significantly to global health and economic challenges. This study elucidated the role of RBM15 in NSCLC progression through its involvement in m6A modifications. Methods RBM15 levels in NSCLC tissues and cells were assessed via RT-qPCR and Western blotting. The impact of RBM15 knockdown on NSCLC proliferation, invasion, and migration was evaluated using CCK-8, colony formation, and Transwell assays. Expression levels of KLF1, TRIM13, and ANXA8 were determined by RT-qPCR and Western blot. m6A methylation levels were analyzed, while RIP and MeRIP assays were employed to explore the interaction between YTHDF1/YTHDF2/m6A and KLF1/TRIM13, as well as KLF1 binding to the ANXA8 promoter. The ubiquitination of ANXA8 was examined through ubiquitination assays. Xenograft and metastasis models were utilized to assess RBM15’s role in vivo. Results RBM15 was found to be overexpressed in NSCLC. Silencing RBM15 led to decreased cell proliferation, invasion, and migration of NSCLC cells. RBM15 upregulated KLF1 and downregulated TRIM13 via YTHDF1/YTHDF2, resulting in the promotion of ANXA8 expression. KLF1 overexpression or TRIM13 downregulation partially reversed the suppressive effects of RBM15 knockdown on NSCLC cell proliferation. ANXA8, upregulated in NSCLC, mitigated the inhibitory effects of RBM15 silencing on malignant behaviors. In vivo, RBM15 downregulation hindered NSCLC cell proliferation and metastasis by modulating the KLF1-TRIM13/ANXA8 axis. Conclusion RBM15-mediated m6A methylation enhances KLF1 expression and suppresses TRIM13 via YTHDF1/YTHDF2, thereby promoting ANXA8 and facilitating NSCLC progression. These findings provide novel insights and potential therapeutic targets for NSCLC treatment. |
| format | Article |
| id | doaj-art-d491dcb9bc0d4fc18b6e4abcdad9dfac |
| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-d491dcb9bc0d4fc18b6e4abcdad9dfac2024-12-29T12:36:12ZengBMCMolecular Medicine1528-36582024-12-0130112010.1186/s10020-024-01018-zRBM15-dependent m6A modification mediates progression of non-small cell lung cancer cellsMan Wang0Yujiao Qin1Xiaoqi Ai2Xiuhua Liu3Department of Respiratory Medicine, The First Affiliated Hospital of Jilin UniversityDepartment of Respiratory Medicine, The First Affiliated Hospital of Jilin UniversityDepartment of Respiratory Medicine, The First Affiliated Hospital of Jilin UniversityDepartment of Respiratory Medicine, The First Affiliated Hospital of Jilin UniversityAbstract Background Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer, contributing significantly to global health and economic challenges. This study elucidated the role of RBM15 in NSCLC progression through its involvement in m6A modifications. Methods RBM15 levels in NSCLC tissues and cells were assessed via RT-qPCR and Western blotting. The impact of RBM15 knockdown on NSCLC proliferation, invasion, and migration was evaluated using CCK-8, colony formation, and Transwell assays. Expression levels of KLF1, TRIM13, and ANXA8 were determined by RT-qPCR and Western blot. m6A methylation levels were analyzed, while RIP and MeRIP assays were employed to explore the interaction between YTHDF1/YTHDF2/m6A and KLF1/TRIM13, as well as KLF1 binding to the ANXA8 promoter. The ubiquitination of ANXA8 was examined through ubiquitination assays. Xenograft and metastasis models were utilized to assess RBM15’s role in vivo. Results RBM15 was found to be overexpressed in NSCLC. Silencing RBM15 led to decreased cell proliferation, invasion, and migration of NSCLC cells. RBM15 upregulated KLF1 and downregulated TRIM13 via YTHDF1/YTHDF2, resulting in the promotion of ANXA8 expression. KLF1 overexpression or TRIM13 downregulation partially reversed the suppressive effects of RBM15 knockdown on NSCLC cell proliferation. ANXA8, upregulated in NSCLC, mitigated the inhibitory effects of RBM15 silencing on malignant behaviors. In vivo, RBM15 downregulation hindered NSCLC cell proliferation and metastasis by modulating the KLF1-TRIM13/ANXA8 axis. Conclusion RBM15-mediated m6A methylation enhances KLF1 expression and suppresses TRIM13 via YTHDF1/YTHDF2, thereby promoting ANXA8 and facilitating NSCLC progression. These findings provide novel insights and potential therapeutic targets for NSCLC treatment.https://doi.org/10.1186/s10020-024-01018-zRBM15NSCLCKLF1TRIM13ANXA8 |
| spellingShingle | Man Wang Yujiao Qin Xiaoqi Ai Xiuhua Liu RBM15-dependent m6A modification mediates progression of non-small cell lung cancer cells Molecular Medicine RBM15 NSCLC KLF1 TRIM13 ANXA8 |
| title | RBM15-dependent m6A modification mediates progression of non-small cell lung cancer cells |
| title_full | RBM15-dependent m6A modification mediates progression of non-small cell lung cancer cells |
| title_fullStr | RBM15-dependent m6A modification mediates progression of non-small cell lung cancer cells |
| title_full_unstemmed | RBM15-dependent m6A modification mediates progression of non-small cell lung cancer cells |
| title_short | RBM15-dependent m6A modification mediates progression of non-small cell lung cancer cells |
| title_sort | rbm15 dependent m6a modification mediates progression of non small cell lung cancer cells |
| topic | RBM15 NSCLC KLF1 TRIM13 ANXA8 |
| url | https://doi.org/10.1186/s10020-024-01018-z |
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