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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
MicroRNA Regulation of Human Breast Cancer Stem Cells
Yohei Shimono1,2, Junko Mukohyama3, Shun-Ichi Nakamura4,5
1Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. yshimono@med.kobe-u.ac.jp.
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.
Insights
MicroRNAs (miRNAs) are key regulators in breast cancer stem cells (CSCs). Dysregulated miRNAs impact stem cell maintenance, differentiation, and disease progression, offering potential therapeutic targets.
Area of Science:
- Molecular Biology
- Cancer Research
- Stem Cell Biology
Background:
- MicroRNAs (miRNAs) regulate fundamental biological processes, including stem cell functions.
- miRNA dysregulation is implicated in various human diseases, notably cancer.
- Breast cancer stem cells (CSCs) play a critical role in tumor initiation and progression.
Purpose of the Study:
- To identify and describe miRNAs differentially expressed in human breast CSCs.
- To explore the role of these miRNAs in regulating CSC maintenance and related pathways.
- To understand miRNA involvement in the distinct phenotype of metastatic breast CSCs.
Main Methods:
- Comparative analysis of miRNA expression profiles between human breast CSCs and non-tumorigenic cancer cells.
- Examination of miRNA expression patterns in normal mammary stem/progenitor cells.
- Review of literature on specific miRNA clusters (e.g., miR-200, miR-183) and their targets in CSCs.
Main Results:
- A set of miRNAs were identified as differentially expressed in human breast CSCs compared to non-tumorigenic cells.
- These miRNAs, including miR-200, miR-183, and let-7 families, target key stem cell maintenance genes and pathways (BMI1, Wnt, Notch).
- Metastatic breast CSCs exhibit distinct phenotypes potentially influenced by specific miRNA regulations.
Conclusions:
- miRNAs are crucial regulators of human breast CSC maintenance, self-renewal, and epithelial-to-mesenchymal transition.
- Understanding miRNA dysregulation in breast CSCs is vital for advancing cancer research and developing targeted therapies.
- Further investigation into miRNA regulation of metastatic CSCs will enhance comprehension of tumor progression.
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