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Sci Rep. 2016 Feb 5;6:19995. doi: 10.1038/srep19995.

miR-203 inhibits proliferation and self-renewal of leukemia stem cells by targeting survivin and Bmi-1.

Author information

1
College of life science and technology, Jinan University, Guangzhou, 510632, P.R. China.
2
Institute of Biomedicine, Jinan University, Guangzhou, 510632, P.R. China.
3
Section of Otolaryngology, Department of Surgery, Yale School of Medicine, U.S.A.
4
Department of Pathological Physiology, Wan-nan Medical College, Wuhu, 241000, P.R. China.
5
College of medicine, Jinan University, Guangzhou, 510632, P.R. China.
6
Department of Pathogen Biology and Immunology, Medical College, Guangdong Pharmaceutical University, Guangzhou 510006, China.
7
Department of Endoscopy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510632, P.R. China.

Abstract

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.

PMID:
26847520
PMCID:
PMC4742816
DOI:
10.1038/srep19995
[Indexed for MEDLINE]
Free PMC Article
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