title: MicroRNA Regulation of Human Breast Cancer Stem Cells.
abstract: MicroRNAs (miRNAs) are involved in virtually all biological processes, including stem cell maintenance, differentiation, and development. The dysregulation of miRNAs is associated with many human diseases including cancer. We have identified a set of miRNAs differentially expressed between human breast cancer stem cells (CSCs) and non-tumorigenic cancer cells. In addition, these miRNAs are similarly upregulated or downregulated in normal mammary stem/progenitor cells. In this review, we mainly describe the miRNAs that are dysregulated in human breast CSCs directly isolated from clinical specimens. The miRNAs and their clusters, such as the miR-200 clusters, miR-183 cluster, miR-221-222 cluster, let-7, miR-142 and miR-214, target the genes and pathways important for stem cell maintenance, such as the self-renewal gene BMI1, apoptosis, Wnt signaling, Notch signaling, and epithelial-to-mesenchymal transition. In addition, the current evidence shows that metastatic breast CSCs acquire a phenotype that is different from the CSCs in a primary site. Thus, clarifying the miRNA regulation of the metastatic breast CSCs will further advance our understanding of the roles of human breast CSCs in tumor progression.
authors.affiliation: Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. yshimono@med.kobe-u.ac.jp.|Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. yshimono@med.kobe-u.ac.jp.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shimono
authors.affiliation: Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. junkom@med.kobe-u.ac.jp.
authors.forename: Junko
authors.initials: J
authors.lastname: Mukohyama
authors.affiliation: Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. snakamur@kobe-u.ac.jp.|Division of Biochemistry, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. snakamur@kobe-u.ac.jp.
authors.forename: Shun-Ichi
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. hminami@med.kobe-u.ac.jp.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Minami
keywords: Bmi1; Wnt signaling; cancer stem cells; epithelial-to-mesenchymal transition (EMT); metastasis; microRNA