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Reduced JAG1 Expression Through miR-200 Overexpression or Crispr-Cas Mediated Knockout Impairs TNBC Growth and

Megan Vaz1, Katrina L Watson1, Roger A Moorehead1

  • 1Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.

Molecular Carcinogenesis
|June 11, 2025
PubMed

Insights

Increasing miR-200 expression in triple-negative breast cancer (TNBC) reduces tumor growth by decreasing JAG1. Targeting JAG1 may offer a new therapeutic strategy for TNBC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Increasing miR-200 expression in triple-negative breast cancer (TNBC) has previously been shown to reduce tumor growth and metastasis.
  • The precise molecular mechanisms by which miR-200 exerts its tumor-suppressive effects in TNBC require further elucidation.

Purpose of the Study:

  • To investigate the role of JAG1 as a downstream target of miR-200 in TNBC.
  • To evaluate the therapeutic potential of targeting JAG1 in TNBC models.

Main Methods:

  • Overexpression of miR-200s in TNBC cell lines.
  • JAG1 gene knockout in MDA-MB-231 cells.
  • In vitro proliferation and invasion assays.
  • In vivo tumor growth and metastasis studies in mouse models.
  • RNA sequencing analysis.

Main Results:

  • Overexpression of miR-200s in TNBC cells led to a significant reduction in JAG1 expression.
  • JAG1 knockout in MDA-MB-231 cells significantly decreased cell proliferation and invasion in vitro.
  • Loss of JAG1 inhibited mammary tumor growth and metastasis in vivo.
  • RNA sequencing revealed that JAG1 loss altered genes involved in extracellular matrix (ECM) remodeling, angiogenesis, and epithelial-mesenchymal transition (EMT).

Conclusions:

  • miR-200 may exert its antitumor effects in TNBC partly by downregulating JAG1 expression.
  • JAG1 inhibition demonstrates therapeutic potential for TNBC.
  • Targeting JAG1 warrants further investigation as a therapeutic strategy for triple-negative breast cancer.
Keywords:
JAG1TNBCbreast cancermetastasismiR‐200

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