Mir-615-3p promotes osteosarcoma progression via the SESN2/AMPK/mTOR pathway
Abstract Background Osteosarcoma (OS) is the most common primary malignant bone neoplasm. Growing researches have highlighted the tumor promoting role of miR-615-3p in various cancers. Notwithstanding, the biological function and underlying mechanisms of miR-615-3p in OS development still unclear. M...
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| Format: | Article |
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BMC
2024-12-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-024-03604-x |
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| author | Xuecheng Yu Xin Wang Fan Xu Xinyi Zhang Muyi Wang Ruikai Zhou Zhengyi Sun Xiaohui Pan Lin Feng Wanchao Zhang Yong Sun Wenting Zhang Dong Zhou Yuqing Jiang |
| author_facet | Xuecheng Yu Xin Wang Fan Xu Xinyi Zhang Muyi Wang Ruikai Zhou Zhengyi Sun Xiaohui Pan Lin Feng Wanchao Zhang Yong Sun Wenting Zhang Dong Zhou Yuqing Jiang |
| author_sort | Xuecheng Yu |
| collection | DOAJ |
| description | Abstract Background Osteosarcoma (OS) is the most common primary malignant bone neoplasm. Growing researches have highlighted the tumor promoting role of miR-615-3p in various cancers. Notwithstanding, the biological function and underlying mechanisms of miR-615-3p in OS development still unclear. Methods Quantitative Real-Time PCR analysis (qRT-PCR) and RNA fluorescence in situ hybridization (FISH) staining were performed to measure miR-615-3p expression in OS. CCK-8 assay, colony formation assay and EdU assay were applied to analyze the OS cell proliferation activity. Cell metastasis abilities were evaluated using Transwell assays. Analysis of apoptosis was performed based on flow cytometric detection. The potential mechanisms of miR-615-3p in OS progression were investigated through RNA immunoprecipitation (RIP) assays, dual-luciferase reporter assays, qRT-PCR and western blotting. In vivo experiments, mouse xenograft model was carried out to assess the tumorigenicity of miR-615-3p. Results This study demonstrated a significant upregulation of miR-615-3p in OS. In addition, miR-615-3p knockdown suppressed OS proliferation, invasion, metastasis and EMT. Mechanistically, miR-615-3p regulated sestrin 2 (SESN2) expression negatively by targeting its 3’UTR. Moreover, silencing SESN2 facilitated OS progression and activated mTOR pathway. Noteworthy, the anticancer functions of miR-615-3p knockdown were partially recovered by SESN2 silencing. Taken together, the miR-615-3p/SESN2/mTOR pathway is critical for regulating OS progression. Conclusion Our results revealed that miR-615-3p modulated mTOR signaling, thus influencing the progression of OS. For OS treatment, molecular strategies that target the miR-615-3p/SESN2/mTOR pathway is promising. |
| format | Article |
| id | doaj-art-924b437564794b979f4fe46289701f6d |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-924b437564794b979f4fe46289701f6d2024-12-22T12:49:14ZengBMCCancer Cell International1475-28672024-12-0124111510.1186/s12935-024-03604-xMir-615-3p promotes osteosarcoma progression via the SESN2/AMPK/mTOR pathwayXuecheng Yu0Xin Wang1Fan Xu2Xinyi Zhang3Muyi Wang4Ruikai Zhou5Zhengyi Sun6Xiaohui Pan7Lin Feng8Wanchao Zhang9Yong Sun10Wenting Zhang11Dong Zhou12Yuqing Jiang13Department of Orthopedics, Changzhou Medical Center, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Orthopedics, Changzhou Medical Center, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Disease Control, 987 Hospital of Joint Logistics Support Force of PLAWenzhou Medical UniversityDepartment of Orthopedics, Changzhou Medical Center, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Orthopedics, Changzhou Medical Center, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Orthopedics, Changzhou Medical Center, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Orthopedics, The Affiliated People’s Hospital of Jiangsu UniversityThe people’s hospital of WuQia countyDepartment of Radiology, The people’s hospital of WuQia countyDepartment of Orthopedics, Wuqia People’s HospitalAffiliated Changzhou Children’s Hospital of Nantong UniversityDepartment of Orthopedics, Changzhou Medical Center, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Orthopedics, Changzhou Medical Center, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Nanjing Medical UniversityAbstract Background Osteosarcoma (OS) is the most common primary malignant bone neoplasm. Growing researches have highlighted the tumor promoting role of miR-615-3p in various cancers. Notwithstanding, the biological function and underlying mechanisms of miR-615-3p in OS development still unclear. Methods Quantitative Real-Time PCR analysis (qRT-PCR) and RNA fluorescence in situ hybridization (FISH) staining were performed to measure miR-615-3p expression in OS. CCK-8 assay, colony formation assay and EdU assay were applied to analyze the OS cell proliferation activity. Cell metastasis abilities were evaluated using Transwell assays. Analysis of apoptosis was performed based on flow cytometric detection. The potential mechanisms of miR-615-3p in OS progression were investigated through RNA immunoprecipitation (RIP) assays, dual-luciferase reporter assays, qRT-PCR and western blotting. In vivo experiments, mouse xenograft model was carried out to assess the tumorigenicity of miR-615-3p. Results This study demonstrated a significant upregulation of miR-615-3p in OS. In addition, miR-615-3p knockdown suppressed OS proliferation, invasion, metastasis and EMT. Mechanistically, miR-615-3p regulated sestrin 2 (SESN2) expression negatively by targeting its 3’UTR. Moreover, silencing SESN2 facilitated OS progression and activated mTOR pathway. Noteworthy, the anticancer functions of miR-615-3p knockdown were partially recovered by SESN2 silencing. Taken together, the miR-615-3p/SESN2/mTOR pathway is critical for regulating OS progression. Conclusion Our results revealed that miR-615-3p modulated mTOR signaling, thus influencing the progression of OS. For OS treatment, molecular strategies that target the miR-615-3p/SESN2/mTOR pathway is promising.https://doi.org/10.1186/s12935-024-03604-xmiR-615-3pSESN2mTOREMTOS |
| spellingShingle | Xuecheng Yu Xin Wang Fan Xu Xinyi Zhang Muyi Wang Ruikai Zhou Zhengyi Sun Xiaohui Pan Lin Feng Wanchao Zhang Yong Sun Wenting Zhang Dong Zhou Yuqing Jiang Mir-615-3p promotes osteosarcoma progression via the SESN2/AMPK/mTOR pathway Cancer Cell International miR-615-3p SESN2 mTOR EMT OS |
| title | Mir-615-3p promotes osteosarcoma progression via the SESN2/AMPK/mTOR pathway |
| title_full | Mir-615-3p promotes osteosarcoma progression via the SESN2/AMPK/mTOR pathway |
| title_fullStr | Mir-615-3p promotes osteosarcoma progression via the SESN2/AMPK/mTOR pathway |
| title_full_unstemmed | Mir-615-3p promotes osteosarcoma progression via the SESN2/AMPK/mTOR pathway |
| title_short | Mir-615-3p promotes osteosarcoma progression via the SESN2/AMPK/mTOR pathway |
| title_sort | mir 615 3p promotes osteosarcoma progression via the sesn2 ampk mtor pathway |
| topic | miR-615-3p SESN2 mTOR EMT OS |
| url | https://doi.org/10.1186/s12935-024-03604-x |
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