miR-150 suppresses the proliferation and tumorigenicity of leukemia stem cells by targeting the Nanog signaling pathway
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 tumorigenici...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-11-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00439/full |
| _version_ | 1798045026554478592 |
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| author | Dan-dan Xu Dan-dan Xu Peng-jun Zhou Peng-jun Zhou Ying Wang Ying Wang Yi Zhang Rong Zhang Li Zhang Su-hong Chen Bi-bo Ruan Hai-peng Xu Wu-yu Fu Chao-zhi Hu Lu Tian Jin-hong Qin Sheng Wang Xiao Wang Qiu-ying Liu Zhe Ren Xue-qui Gu Yao-he Li Zhong Liu Yi Fei Wang |
| author_facet | Dan-dan Xu Dan-dan Xu Peng-jun Zhou Peng-jun Zhou Ying Wang Ying Wang Yi Zhang Rong Zhang Li Zhang Su-hong Chen Bi-bo Ruan Hai-peng Xu Wu-yu Fu Chao-zhi Hu Lu Tian Jin-hong Qin Sheng Wang Xiao Wang Qiu-ying Liu Zhe Ren Xue-qui Gu Yao-he Li Zhong Liu Yi Fei Wang |
| author_sort | Dan-dan Xu |
| collection | DOAJ |
| description | 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 tumour 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 behaviour 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. |
| first_indexed | 2024-04-11T23:13:54Z |
| format | Article |
| id | doaj.art-13d0542b87954cf5a1703a1a118cd2bd |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T23:13:54Z |
| publishDate | 2016-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-13d0542b87954cf5a1703a1a118cd2bd2022-12-22T03:57:42ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122016-11-01710.3389/fphar.2016.00439205435miR-150 suppresses the proliferation and tumorigenicity of leukemia stem cells by targeting the Nanog signaling pathwayDan-dan Xu0Dan-dan Xu1Peng-jun Zhou2Peng-jun Zhou3Ying Wang4Ying Wang5Yi Zhang6Rong Zhang7Li Zhang8Su-hong Chen9Bi-bo Ruan10Hai-peng Xu11Wu-yu Fu12Chao-zhi Hu13Lu Tian14Jin-hong Qin15Sheng Wang16Xiao Wang17Qiu-ying Liu18Zhe Ren19Xue-qui Gu20Yao-he Li21Zhong Liu22Yi Fei Wang23College of life science and technology, Jinan UniversitySchool of Biology Technolgy, Guangdong Food and Drug Vocational CollegeCollege of life science and technology, Jinan UniversitySchool of Basic Course, Guangdong Pharmaceutical UniversityCollege of life science and technology, Jinan UniversityFaculty of Environmental and Biological Engineering, Guangdong University of Petrochemical TechnologySection of Otolaryngology, Department of Surgery, Yale School of MedicineState Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterCollege of life science and technology, Jinan UniversitySchool of Biology Technolgy, Guangdong Food and Drug Vocational CollegeSchool of Basic Course, Guangdong Pharmaceutical UniversityCollege of life science and technology, Jinan UniversitySchool of Basic Course, Guangdong Pharmaceutical UniversityCollege of life science and technology, Jinan UniversityCollege of life science and technology, Jinan UniversityCollege of life science and technology, Jinan UniversityCollege of life science and technology, Jinan UniversityCollege of life science and technology, Jinan UniversityCollege of life science and technology, Jinan UniversityCollege of life science and technology, Jinan Universitythe First Affiliated Hospital of Guangdong Traditional Medicine Universitythe First Affiliated Hospital of Guangdong Traditional Medicine UniversityCollege of life science and technology, Jinan UniversityCollege of life science and technology, Jinan UniversityProliferation, 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 tumour 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 behaviour 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.http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00439/fullproliferationnanogLeukemia Stem CellsTumorigenicityMiR-150 |
| spellingShingle | Dan-dan Xu Dan-dan Xu Peng-jun Zhou Peng-jun Zhou Ying Wang Ying Wang Yi Zhang Rong Zhang Li Zhang Su-hong Chen Bi-bo Ruan Hai-peng Xu Wu-yu Fu Chao-zhi Hu Lu Tian Jin-hong Qin Sheng Wang Xiao Wang Qiu-ying Liu Zhe Ren Xue-qui Gu Yao-he Li Zhong Liu Yi Fei Wang miR-150 suppresses the proliferation and tumorigenicity of leukemia stem cells by targeting the Nanog signaling pathway Frontiers in Pharmacology proliferation nanog Leukemia Stem Cells Tumorigenicity MiR-150 |
| title | miR-150 suppresses the proliferation and tumorigenicity of leukemia stem cells by targeting the Nanog signaling pathway |
| title_full | miR-150 suppresses the proliferation and tumorigenicity of leukemia stem cells by targeting the Nanog signaling pathway |
| title_fullStr | miR-150 suppresses the proliferation and tumorigenicity of leukemia stem cells by targeting the Nanog signaling pathway |
| title_full_unstemmed | miR-150 suppresses the proliferation and tumorigenicity of leukemia stem cells by targeting the Nanog signaling pathway |
| title_short | miR-150 suppresses the proliferation and tumorigenicity of leukemia stem cells by targeting the Nanog signaling pathway |
| title_sort | mir 150 suppresses the proliferation and tumorigenicity of leukemia stem cells by targeting the nanog signaling pathway |
| topic | proliferation nanog Leukemia Stem Cells Tumorigenicity MiR-150 |
| url | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00439/full |
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