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Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...

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Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization
06:01

Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization

Published on: June 7, 2016

Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells.

Yohei Shimono1, Maider Zabala, Robert W Cho

  • 1Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, 1050 Arastradero Road, Palo Alto, CA 94304, USA.

Cell
|August 12, 2009
PubMed
Summary

MicroRNAs like miR-200c are downregulated in breast cancer stem cells (BCSCs). This microRNA inhibits cancer cell growth and stem cell self-renewal, linking BCSCs to normal stem cells.

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Area of Science:

  • Molecular Biology
  • Cancer Stem Cell Research
  • MicroRNA Biology

Background:

  • Human breast tumors harbor cancer stem cells (BCSCs) with stem cell-like properties.
  • MicroRNAs (miRNAs) play crucial roles in regulating gene expression and cellular processes.
  • Understanding the molecular mechanisms governing BCSCs is vital for developing effective cancer therapies.

Purpose of the Study:

  • To identify differentially expressed microRNAs between human BCSCs and non-tumorigenic cancer cells.
  • To investigate the role of specific microRNA clusters, particularly the miR-200 family, in regulating stem cell properties.
  • To explore the functional impact of miR-200c on breast cancer cell proliferation and stem cell behavior in vitro and in vivo.

Main Methods:

  • Differential expression analysis of microRNAs in human BCSCs and non-tumorigenic cancer cells.
  • In vitro functional assays to assess the effect of miR-200c on cancer cell clonal expansion and embryonal carcinoma cell growth.
  • In vivo studies using mouse models to evaluate the impact of miR-200c on mammary stem cell function and BCSC-driven tumor formation.

Main Results:

  • Thirty-seven microRNAs were found to be differentially expressed between human BCSCs and non-tumorigenic cancer cells.
  • Three microRNA clusters (miR-200c-141, miR-200b-200a-429, miR-183-96-182) were downregulated in BCSCs, normal mammary stem cells, and embryonal carcinoma cells.
  • miR-200c inhibited breast cancer cell proliferation, suppressed embryonal carcinoma cell growth, and crucially, reduced mammary duct formation and BCSC-driven tumor growth in vivo.
  • BMI1, a stem cell self-renewal regulator, was modulated by miR-200c.

Conclusions:

  • The coordinated downregulation of specific microRNA clusters, including miR-200c, is a key feature connecting breast cancer stem cells with normal stem cells.
  • miR-200c acts as a tumor suppressor by inhibiting cancer stem cell self-renewal and tumor formation.
  • These findings provide a molecular link between BCSCs and normal stem cells, highlighting the therapeutic potential of targeting microRNAs in breast cancer treatment.