title: miR-150 Suppresses the Proliferation and Tumorigenicity of Leukemia Stem Cells by Targeting the Nanog Signaling Pathway.
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 LSCsin 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.
authors.affiliation: College of Life Science and Technology, Jinan UniversityGuangzhou, China; College of Biology Technolgy, Guangdong Food and Drug Vocational CollegeGuangzhou, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Xu
authors.affiliation: College of Life Science and Technology, Jinan University Guangzhou, China.
authors.forename: Peng-Jun
authors.initials: PJ
authors.lastname: Zhou
authors.affiliation: College of Life Science and Technology, Jinan UniversityGuangzhou, China; Faculty of Environmental and Biological Engineering, Guangdong University of Petrochemical TechnologyMaoming, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Section of Otolaryngology, Department of Surgery, Yale School of Medicine, New Haven CT, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center Guangzhou, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: College of Life Science and Technology, Jinan University Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Biology Technolgy, Guangdong Food and Drug Vocational College Guangzhou, China.
authors.forename: Su-Hong
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Faculty of Environmental and Biological Engineering, Guangdong University of Petrochemical Technology Maoming, China.
authors.forename: Wu-Yu
authors.initials: WY
authors.lastname: Fu
authors.affiliation: Faculty of Environmental and Biological Engineering, Guangdong University of Petrochemical Technology Maoming, China.
authors.forename: Bi-Bo
authors.initials: BB
authors.lastname: Ruan
authors.affiliation: College of Life Science and Technology, Jinan University Guangzhou, China.
authors.forename: Hai-Peng
authors.initials: HP
authors.lastname: Xu
authors.affiliation: College of Life Science and Technology, Jinan University Guangzhou, China.
authors.forename: Chao-Zhi
authors.initials: CZ
authors.lastname: Hu
authors.affiliation: College of Life Science and Technology, Jinan University Guangzhou, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Tian
authors.affiliation: College of Life Science and Technology, Jinan University Guangzhou, China.
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Qin
authors.affiliation: College of Life Science and Technology, Jinan University Guangzhou, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: College of Life Science and Technology, Jinan University Guangzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Life Science and Technology, Jinan University Guangzhou, China.
authors.forename: Qiu-Ying
authors.initials: QY
authors.lastname: Liu
authors.affiliation: College of Life Science and Technology, Jinan University Guangzhou, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ren
authors.affiliation: The First Affiliated Hospital, Guangzhou Hospital of Traditional Chinese Medicine Guangzhou, China.
authors.forename: Xue-Kui
authors.initials: XK
authors.lastname: Gu
authors.affiliation: The First Affiliated Hospital, Guangzhou Hospital of Traditional Chinese Medicine Guangzhou, China.
authors.forename: Yao-He
authors.initials: YH
authors.lastname: Li
authors.affiliation: College of Life Science and Technology, Jinan University Guangzhou, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Life Science and Technology, Jinan University Guangzhou, China.
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Wang
keywords: Nanog; leukemia stem cells; miR-150; proliferation; tumorigenicity