| Autor: |
Rui Su, Chuting Li, Xiuyuan Wang, Zhendong Li, Ziqi Wen, Zhao Yin, Guiping Huang, Yanjun Liu, Juhua Yang, Haiyan Hu, Hong Nie, Keda Zhang, Jia Fei |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Nucleic Acids, Vol 32, Iss , Pp 729-742 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2162-2531 |
| DOI: |
10.1016/j.omtn.2023.04.026 |
| Popis: |
A large proportion of patients with chronic myeloid leukemia (CML; 20%–50%) develop resistance to imatinib in a BCR-ABL1-independent manner. Therefore, new therapeutic strategies for use in this subset of imatinib-resistant CML patients are urgently needed. In this study, we used a multi-omics approach to show that PPFIA1 was targeted by miR-181a. We demonstrate that both miR-181a and PPFIA1-siRNA reduced the cell viability and proliferative capacity of CML cells in vitro, as well as prolonged the survival of B-NDG mice harboring human BCR-ABL1-independent imatinib-resistant CML cells. Furthermore, treatment with miR-181a mimic and PPFIA1-siRNA inhibited the self-renewal of c-kit+ and CD34+ leukemic stem cells and promoted their apoptosis. Small activating (sa)RNAs targeting the promoter of miR-181a increased the expression of endogenous primitive miR-181a (pri-miR-181a). Transfection with saRNA 1–3 inhibited the proliferation of imatinib-sensitive and -resistant CML cells. However, only saRNA-3 showed a stronger and more sustained inhibitory effect than the miR-181a mimic. Collectively, these results show that miR-181a and PPFIA1-siRNA may overcome the imatinib resistance of BCR-ABL1-independent CML, partially by inhibiting the self-renewal of leukemia stem cells and promoting their apoptosis. Moreover, exogenous saRNAs represent promising therapeutic agents in the treatment of imatinib-resistant BCR-ABL1-independent CML. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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