Exosome-Transmitted tRF-16-K8J7K1B Promotes Tamoxifen Resistance by Reducing Drug-Induced Cell Apoptosis in Breast Cancer
Tamoxifen resistance remains a challenge in hormone receptor-positive (HR+) breast cancer. Recent evidence suggests that transfer ribonucleic acid (tRNA)-derived fragments play pivotal roles in the occurrence and development of various tumors. However, the relationship between tRNA-derived fragments...
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MDPI AG
2023-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/3/899 |
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| author | Chunxiao Sun Xiang Huang Jun Li Ziyi Fu Yijia Hua Tianyu Zeng Yaozhou He Ningjun Duan Fan Yang Yan Liang Hao Wu Wei Li Yuchen Zhang Yongmei Yin |
| author_facet | Chunxiao Sun Xiang Huang Jun Li Ziyi Fu Yijia Hua Tianyu Zeng Yaozhou He Ningjun Duan Fan Yang Yan Liang Hao Wu Wei Li Yuchen Zhang Yongmei Yin |
| author_sort | Chunxiao Sun |
| collection | DOAJ |
| description | Tamoxifen resistance remains a challenge in hormone receptor-positive (HR+) breast cancer. Recent evidence suggests that transfer ribonucleic acid (tRNA)-derived fragments play pivotal roles in the occurrence and development of various tumors. However, the relationship between tRNA-derived fragments and tamoxifen resistance remains unclear. In this study, we found that the expression of tRF-16-K8J7K1B was upregulated in tamoxifen-resistant cells in comparison with tamoxifen-sensitive cells. Higher levels of tRF-16-K8J7K1B were associated with shorter disease-free survival in HR+ breast cancer. Overexpression of tRF-16-K8J7K1B promotes tamoxifen resistance. Moreover, extracellular tRF-16-K8J7K1B could be packaged into exosomes and could disseminate tamoxifen resistance to recipient cells. Mechanistically, exosomal tRF-16-K8J7K1B downregulates the expression of apoptosis-related proteins, such as caspase 3 and poly (ADP-ribose) polymerase, by targeting tumor necrosis factor-related apoptosis-inducing ligand in receptor cells, thereby reducing drug-induced cell apoptosis. Therapeutically, the inhibition of exosomal tRF-16-K8J7K1B increases the sensitivity of breast cancer cells to tamoxifen in vivo. These data demonstrate that exosomal tRF-16-K8J7K1B may be a novel therapeutic target to overcome tamoxifen resistance in HR+ breast cancer. |
| first_indexed | 2024-03-11T09:50:33Z |
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| id | doaj.art-e570d95a4dfe4832820544b79f1e26b3 |
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| language | English |
| last_indexed | 2024-03-11T09:50:33Z |
| publishDate | 2023-01-01 |
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| series | Cancers |
| spelling | doaj.art-e570d95a4dfe4832820544b79f1e26b32023-11-16T16:18:47ZengMDPI AGCancers2072-66942023-01-0115389910.3390/cancers15030899Exosome-Transmitted tRF-16-K8J7K1B Promotes Tamoxifen Resistance by Reducing Drug-Induced Cell Apoptosis in Breast CancerChunxiao Sun0Xiang Huang1Jun Li2Ziyi Fu3Yijia Hua4Tianyu Zeng5Yaozhou He6Ningjun Duan7Fan Yang8Yan Liang9Hao Wu10Wei Li11Yuchen Zhang12Yongmei Yin13Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaThe First Clinical College, Nanjing Medical University, Nanjing 210029, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaTamoxifen resistance remains a challenge in hormone receptor-positive (HR+) breast cancer. Recent evidence suggests that transfer ribonucleic acid (tRNA)-derived fragments play pivotal roles in the occurrence and development of various tumors. However, the relationship between tRNA-derived fragments and tamoxifen resistance remains unclear. In this study, we found that the expression of tRF-16-K8J7K1B was upregulated in tamoxifen-resistant cells in comparison with tamoxifen-sensitive cells. Higher levels of tRF-16-K8J7K1B were associated with shorter disease-free survival in HR+ breast cancer. Overexpression of tRF-16-K8J7K1B promotes tamoxifen resistance. Moreover, extracellular tRF-16-K8J7K1B could be packaged into exosomes and could disseminate tamoxifen resistance to recipient cells. Mechanistically, exosomal tRF-16-K8J7K1B downregulates the expression of apoptosis-related proteins, such as caspase 3 and poly (ADP-ribose) polymerase, by targeting tumor necrosis factor-related apoptosis-inducing ligand in receptor cells, thereby reducing drug-induced cell apoptosis. Therapeutically, the inhibition of exosomal tRF-16-K8J7K1B increases the sensitivity of breast cancer cells to tamoxifen in vivo. These data demonstrate that exosomal tRF-16-K8J7K1B may be a novel therapeutic target to overcome tamoxifen resistance in HR+ breast cancer.https://www.mdpi.com/2072-6694/15/3/899breast cancertamoxifen resistancetRNA-derived fragmentsexosomes |
| spellingShingle | Chunxiao Sun Xiang Huang Jun Li Ziyi Fu Yijia Hua Tianyu Zeng Yaozhou He Ningjun Duan Fan Yang Yan Liang Hao Wu Wei Li Yuchen Zhang Yongmei Yin Exosome-Transmitted tRF-16-K8J7K1B Promotes Tamoxifen Resistance by Reducing Drug-Induced Cell Apoptosis in Breast Cancer Cancers breast cancer tamoxifen resistance tRNA-derived fragments exosomes |
| title | Exosome-Transmitted tRF-16-K8J7K1B Promotes Tamoxifen Resistance by Reducing Drug-Induced Cell Apoptosis in Breast Cancer |
| title_full | Exosome-Transmitted tRF-16-K8J7K1B Promotes Tamoxifen Resistance by Reducing Drug-Induced Cell Apoptosis in Breast Cancer |
| title_fullStr | Exosome-Transmitted tRF-16-K8J7K1B Promotes Tamoxifen Resistance by Reducing Drug-Induced Cell Apoptosis in Breast Cancer |
| title_full_unstemmed | Exosome-Transmitted tRF-16-K8J7K1B Promotes Tamoxifen Resistance by Reducing Drug-Induced Cell Apoptosis in Breast Cancer |
| title_short | Exosome-Transmitted tRF-16-K8J7K1B Promotes Tamoxifen Resistance by Reducing Drug-Induced Cell Apoptosis in Breast Cancer |
| title_sort | exosome transmitted trf 16 k8j7k1b promotes tamoxifen resistance by reducing drug induced cell apoptosis in breast cancer |
| topic | breast cancer tamoxifen resistance tRNA-derived fragments exosomes |
| url | https://www.mdpi.com/2072-6694/15/3/899 |
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