机构：[1]College of Life Science and Technology, Jinan University, Guangzhou, China[2]College of Biology Technolgy, Guangdong Food and Drug Vocational College, Guangzhou, China[3]Faculty of Environmental and Biological Engineering, Guangdong University of Petrochemical Technology, Maoming, 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]The First Affiliated Hospital, Guangzhou Hospital of Traditional Chinese Medicine, Guangzhou, China
Proliferation, a key feature of cancer cells, accounts for the majority of cancerrelated diseases resulting in mortality. MicroRNAs (miRNAs) plays important posttranscriptional 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.
基金：
Administration of Ocean and Fisheries of Guangdong Province Program [A1201301C06, GD2013-B02-003]; Science and Technology Program of Guangzhou, China [201610010108, 201300000041]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [21615410, 21615413]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2015M572414]
第一作者机构：[1]College of Life Science and Technology, Jinan University, Guangzhou, China[2]College of Biology Technolgy, Guangdong Food and Drug Vocational College, Guangzhou, China
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推荐引用方式(GB/T 7714)：
Xu Dan-dan,Zhou Peng-jun,Wang Ying,et al.miR-150 Suppresses the Proliferation and Tumorigenicity of Leukemia Stem Cells by Targeting the Nanog Signaling Pathway[J].FRONTIERS IN PHARMACOLOGY.2016,7:doi:10.3389/fphar.2016.00439.
APA：
Xu, Dan-dan,Zhou, Peng-jun,Wang, Ying,Zhang, Yi,Zhang, Rong...&Wang, Yi-fei.(2016).miR-150 Suppresses the Proliferation and Tumorigenicity of Leukemia Stem Cells by Targeting the Nanog Signaling Pathway.FRONTIERS IN PHARMACOLOGY,7,
MLA：
Xu, Dan-dan,et al."miR-150 Suppresses the Proliferation and Tumorigenicity of Leukemia Stem Cells by Targeting the Nanog Signaling Pathway".FRONTIERS IN PHARMACOLOGY 7.(2016)
