miR-203 inhibits proliferation and self-renewal of leukemia stem cells by targeting survivin and Bmi-1
| Autor: | Hai Xuan Chen, Dong Lei Ma, Qiu Ying Liu, Bi Bo Ruan, Wang Yifei, Yi Zhang, Peng Jun Zhou, Zhe Ren, Dan-Dan Xu, Hai Zhao Yan, Yuting Liu, Shu Yan Zhou, Wu Yu Fu, Sheng Wang, Rong Zhang, Ying Wang, Xiaoyan Wang, Li Zhang, Xiao Wang, Zhong Liu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Myeloid Survivin Down-Regulation Mice Nude Antigens CD34 Biology Real-Time Polymerase Chain Reaction medicine.disease_cause Article Inhibitor of Apoptosis Proteins Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor microRNA medicine Animals Humans RNA Messenger RNA Small Interfering 3' Untranslated Regions Cell Proliferation Polycomb Repressive Complex 1 Multidisciplinary Base Sequence Myeloid leukemia medicine.disease Cell biology Leukemia Myeloid Acute MicroRNAs Leukemia 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Neoplastic Stem Cells Cancer research RNA Interference Stem cell Carcinogenesis miR-203 Sequence Alignment |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep19995 |
| Popis: | Drug resistance is one of the leading causes of failed cancer therapy in the treatment of acute myeloid leukemia. Although the mechanisms of resistance are poorly understood, they may be related to the presence of leukemia stem cells (LSCs). Down-regulation of the miR-203 reportedly contributes to oncogenesis and chemo-resistance in multiple cancers. We found that miR-203 expression was down-regulated in CD34 + AML cells as compared with CD34− cells isolated from patients as well as in LSC-enriched (CD34 + CD38−) cell lines KG-1a or MOLM13. Additionally, re-expression of miR-203 led to decreased cell proliferation, self-renewal and sphere formation in LSCs. Moreover, miR-203 was found to directly target the 3′un-translated regions of survivin and Bmi-1 mRNAs affecting proliferation and self-renewal in LSCs. In this study, we identified a novel miR-203/survivin/Bmi-1 axis involved in the regulation of biological properties of LSCs. This axis may represent a new therapeutic target for acute myeloid leukemia and a potential prognosis/diagnostic marker for LSCs therapy. |
| Databáze: | OpenAIRE |
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