Aberrantly reduced expression of miR-342-5p contributes to CCND1-associated chronic myeloid leukemia progression and imatinib resistance
Abstract Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome, and the current standard of care is the use of tyrosine kinase inhibitors (TKI). However, some patients will not achieve a molecular response and may progress to blast crisis, and th...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-10-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-04209-2 |
| _version_ | 1819118128206970880 |
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| author | Yi-Ying Wu Hsing-Fan Lai Tzu-Chuan Huang Yu-Guang Chen Ren-Hua Ye Ping-Ying Chang Shiue-Wei Lai Yeu-Chin Chen Cho-Hao Lee Wei-Nung Liu Ming-Shen Dai Jia-Hong Chen Ching-Liang Ho Yi-Lin Chiu |
| author_facet | Yi-Ying Wu Hsing-Fan Lai Tzu-Chuan Huang Yu-Guang Chen Ren-Hua Ye Ping-Ying Chang Shiue-Wei Lai Yeu-Chin Chen Cho-Hao Lee Wei-Nung Liu Ming-Shen Dai Jia-Hong Chen Ching-Liang Ho Yi-Lin Chiu |
| author_sort | Yi-Ying Wu |
| collection | DOAJ |
| description | Abstract Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome, and the current standard of care is the use of tyrosine kinase inhibitors (TKI). However, some patients will not achieve a molecular response and may progress to blast crisis, and the underlying mechanisms remain to be clarified. In this study, next-generation sequencing was used to explore endogenous miRNAs in CML patients versus healthy volunteers, and miR-342-5p was identified as the primary target. We found that miR-342-5p was downregulated in CML patients and had a significant inhibitory effect on cell proliferation in CML. Through a luciferase reporter system, miR-342-5p was reported to target the 3’-UTR domain of CCND1 and downregulated its expression. Furthermore, overexpression of miR-342-5p enhanced imatinib-induced DNA double-strand breaks and apoptosis. Finally, by analyzing clinical databases, we further confirmed that miR-342-5p was associated with predicted molecular responses in CML patients. In conclusion, we found that both in vivo and in vitro experiments and database cohorts showed that miR-342-5p plays a key role in CML patients, indicating that miR-342-5p may be a potential target for future CML treatment or prognostic evaluation. |
| first_indexed | 2024-12-22T05:43:57Z |
| format | Article |
| id | doaj.art-83c483f329e9417f8d63a0c095d3e314 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-22T05:43:57Z |
| publishDate | 2021-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-83c483f329e9417f8d63a0c095d3e3142022-12-21T18:37:06ZengNature Publishing GroupCell Death and Disease2041-48892021-10-01121011210.1038/s41419-021-04209-2Aberrantly reduced expression of miR-342-5p contributes to CCND1-associated chronic myeloid leukemia progression and imatinib resistanceYi-Ying Wu0Hsing-Fan Lai1Tzu-Chuan Huang2Yu-Guang Chen3Ren-Hua Ye4Ping-Ying Chang5Shiue-Wei Lai6Yeu-Chin Chen7Cho-Hao Lee8Wei-Nung Liu9Ming-Shen Dai10Jia-Hong Chen11Ching-Liang Ho12Yi-Lin Chiu13Division of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDepartment of Biochemistry, National Defense Medical CenterDivision of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDivision of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDivision of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDivision of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDivision of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDivision of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDivision of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDivision of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDivision of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDivision of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDivision of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDepartment of Biochemistry, National Defense Medical CenterAbstract Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome, and the current standard of care is the use of tyrosine kinase inhibitors (TKI). However, some patients will not achieve a molecular response and may progress to blast crisis, and the underlying mechanisms remain to be clarified. In this study, next-generation sequencing was used to explore endogenous miRNAs in CML patients versus healthy volunteers, and miR-342-5p was identified as the primary target. We found that miR-342-5p was downregulated in CML patients and had a significant inhibitory effect on cell proliferation in CML. Through a luciferase reporter system, miR-342-5p was reported to target the 3’-UTR domain of CCND1 and downregulated its expression. Furthermore, overexpression of miR-342-5p enhanced imatinib-induced DNA double-strand breaks and apoptosis. Finally, by analyzing clinical databases, we further confirmed that miR-342-5p was associated with predicted molecular responses in CML patients. In conclusion, we found that both in vivo and in vitro experiments and database cohorts showed that miR-342-5p plays a key role in CML patients, indicating that miR-342-5p may be a potential target for future CML treatment or prognostic evaluation.https://doi.org/10.1038/s41419-021-04209-2 |
| spellingShingle | Yi-Ying Wu Hsing-Fan Lai Tzu-Chuan Huang Yu-Guang Chen Ren-Hua Ye Ping-Ying Chang Shiue-Wei Lai Yeu-Chin Chen Cho-Hao Lee Wei-Nung Liu Ming-Shen Dai Jia-Hong Chen Ching-Liang Ho Yi-Lin Chiu Aberrantly reduced expression of miR-342-5p contributes to CCND1-associated chronic myeloid leukemia progression and imatinib resistance Cell Death and Disease |
| title | Aberrantly reduced expression of miR-342-5p contributes to CCND1-associated chronic myeloid leukemia progression and imatinib resistance |
| title_full | Aberrantly reduced expression of miR-342-5p contributes to CCND1-associated chronic myeloid leukemia progression and imatinib resistance |
| title_fullStr | Aberrantly reduced expression of miR-342-5p contributes to CCND1-associated chronic myeloid leukemia progression and imatinib resistance |
| title_full_unstemmed | Aberrantly reduced expression of miR-342-5p contributes to CCND1-associated chronic myeloid leukemia progression and imatinib resistance |
| title_short | Aberrantly reduced expression of miR-342-5p contributes to CCND1-associated chronic myeloid leukemia progression and imatinib resistance |
| title_sort | aberrantly reduced expression of mir 342 5p contributes to ccnd1 associated chronic myeloid leukemia progression and imatinib resistance |
| url | https://doi.org/10.1038/s41419-021-04209-2 |
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