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Front Pharmacol. 2016 Nov 18;7:439. eCollection 2016.

miR-150 Suppresses the Proliferation and Tumorigenicity of Leukemia Stem Cells by Targeting the Nanog Signaling Pathway.

Author information

1
College of Life Science and Technology, Jinan UniversityGuangzhou, China; College of Biology Technolgy, Guangdong Food and Drug Vocational CollegeGuangzhou, China.
2
College of Life Science and Technology, Jinan University Guangzhou, China.
3
College of Life Science and Technology, Jinan UniversityGuangzhou, China; Faculty of Environmental and Biological Engineering, Guangdong University of Petrochemical TechnologyMaoming, China.
4
Section of Otolaryngology, Department of Surgery, Yale School of Medicine, New Haven CT, USA.
5
State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center Guangzhou, China.
6
College of Biology Technolgy, Guangdong Food and Drug Vocational College Guangzhou, China.
7
Faculty of Environmental and Biological Engineering, Guangdong University of Petrochemical Technology Maoming, China.
8
The First Affiliated Hospital, Guangzhou Hospital of Traditional Chinese Medicine Guangzhou, China.

Abstract

Proliferation, a key feature of cancer cells, accounts for the majority of cancer-related diseases resulting in mortality. MicroRNAs (miRNAs) plays important post-transcriptional modulation roles by acting on multiple signaling pathways, but the underlying mechanism in proliferation and tumorigenicity is unclear. Here, we identified the role of miR-150 in proliferation and tumorigenicity in leukemia stem cells (LSCs; CD34+CD38- cells). miR-150 expression was significantly down-regulated in LSCs from leukemia cell lines and clinical samples. Functional assays demonstrated that increased miR-150 expression inhibited proliferation and clonal and clonogenic growth, enhanced chemosensitivity, and attenuated tumorigenic activity of LSCs in vitro. Transplantation animal studies revealed that miR-150 overexpression progressively abrogates tumor growth. Immunohistochemistry assays demonstrated that miR-150 overexpression enhanced caspase-3 level and reduced Ki-67 level. Moreover, luciferase reporter assays indicated Nanog is a direct and functional target of miR-150. Nanog silencing using small interfering RNA recapitulated anti-proliferation and tumorigenicity inhibition effects. Furthermore, miR-150 directly down-regulated the expression of other cancer stem cell factors including Notch2 and CTNNB1. These results provide insights into the specific biological behavior of miR-150 in regulating LSC proliferation and tumorigenicity. Targeting this miR-150/Nanog axis would be a helpful therapeutic strategy to treat acute myeloid leukemia.

KEYWORDS:

Nanog; leukemia stem cells; miR-150; proliferation; tumorigenicity

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