Academic Journal
MicroRNA93 Regulates Proliferation and Differentiation of Normal and Malignant Breast Stem Cells
| العنوان: | MicroRNA93 Regulates Proliferation and Differentiation of Normal and Malignant Breast Stem Cells |
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| المؤلفون: | Liu, Suling, Patel, Shivani H., Ginestier, Christophe, Ibarra, Ingrid, Martin-Trevino, Rachel, Bai, Shoumin, Mcdermott, Sean P., Shang, Li, Ke, Jia, Ou, Sing J., Heath, Amber, Zhang, Kevin J., Korkaya, Hasan, Clouthier, Shawn G., Charafe-Jauffret, Emmanuelle, Birnbaum, Daniel, Hannon, Gregory J., Wicha, Max S. |
| المساهمون: | Department of Internal Medicine, University of Michigan Ann Arbor, University of Michigan System-University of Michigan System, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC), Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Program in Genetics and Bioinformatics Cold Spring Harbor, NY, USA, Cold Spring Harbor Laboratory (CSHL), Institut Paoli-Calmettes (IPC), Fédération nationale des Centres de lutte contre le Cancer (FNCLCC) |
| المصدر: | ISSN: 1553-7390. |
| بيانات النشر: | HAL CCSD Public Library of Science |
| سنة النشر: | 2012 |
| المجموعة: | Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| مصطلحات موضوعية: | Cancer treatment, MicroRNAs, Cancer stem cells, Breast cancer, Metastasis, Tumor stem cells, Cell differentiation, Stem cells, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] |
| الوصف: | International audience ; MicroRNAs (miRNAs) play important roles in normal cellular differentiation and oncogenesis. microRNA93 (mir-93), a member of the mir106b-25 cluster, located in intron 13 of the MCM7 gene, although frequently overexpressed in human malignancies may also function as a tumor suppressor gene. Using a series of breast cancer cell lines representing different stages of differentiation and mouse xenograft models, we demonstrate that mir-93 modulates the fate of breast cancer stem cells (BCSCs) by regulating their proliferation and differentiation states. In ``claudin(low)'' SUM159 cells, expression of mir-93 induces Mesenchymal-Epithelial Transition (MET) associated with downregulation of TGF beta signaling and downregulates multiple stem cell regulatory genes, including JAK1, STAT3, AKT3, SOX4, EZH1, and HMGA2, resulting in cancer stem cell (CSC) depletion. Enforced expression of mir-93 completely blocks tumor development in mammary fat pads and development of metastases following intracardiac injection in mouse xenografts. The effect of mir-93 on the CSC population is dependent on the cellular differentiation state, with mir-93 expression increasing the CSC population in MCF7 cells that display a more differentiated ``luminal'' phenotype. mir-93 also regulates the proliferation and differentiation of normal breast stem cells isolated from reduction mammoplasties. These studies demonstrate that miRNAs can regulate the states and fates of normal and malignant mammary stem cells, findings which have important biological and clinical implications. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | hal-01431938; https://hal.science/hal-01431938; https://hal.science/hal-01431938/document; https://hal.science/hal-01431938/file/journal.pgen.1002751.PDF |
| DOI: | 10.1371/journal.pgen.1002751 |
| الاتاحة: | https://hal.science/hal-01431938 https://hal.science/hal-01431938/document https://hal.science/hal-01431938/file/journal.pgen.1002751.PDF https://doi.org/10.1371/journal.pgen.1002751 |
| Rights: | http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.55751FC0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.pgen.1002751 |
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