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The Use of Mouse Mammary Tumor Cells in an In Vitro Invasion Assay as a Measure of Oncogenic Cell Behavior
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A MicroRNA/Ubiquitin Ligase Feedback Loop Regulates Slug-Mediated Invasion in Breast Cancer

Rajesh Kumar Manne1, Yashika Agrawal1, Anil Bargale2

  • 1National Centre for Cell Science, Pune University Campus, Ganesh khind, Pune, 411 007, Maharashtra, India.

Neoplasia (New York, N.Y.)
|May 14, 2017
PubMed

Insights

Oncogenic microRNAs miR-93 and miR-106a repress the tumor suppressor FBXO31, promoting cancer cell invasion. This creates a feedback loop where Slug upregulates these microRNAs, driving tumor growth.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Cancer development involves the disruption of normal cellular signaling pathways.
  • The tumor suppressor FBXO31, part of the SCF E3 ubiquitin ligase, normally halts cell growth after DNA damage.
  • FBXO31 is often underexpressed in cancers, but the mechanisms regulating its translation are not fully understood.

Purpose of the Study:

  • To elucidate the translational regulation of the tumor suppressor FBXO31.
  • To investigate the role of microRNAs in controlling FBXO31 levels and its impact on cancer progression.

Main Methods:

  • Investigated the interaction between microRNAs (miR-93, miR-106a) and FBXO31.
  • Analyzed the ubiquitination and degradation of Slug by FBXO31.
  • Examined the feedback loop between Slug and microRNAs in breast tumor samples.

Main Results:

  • Oncogenic microRNAs miR-93 and miR-106a were found to repress FBXO31 translation.
  • FBXO31 targets and promotes the degradation of Slug, a protein involved in cell invasion.
  • Slug was shown to drive the expression of miR-93 and miR-106a, forming a positive feedback loop.
  • This regulatory loop is disrupted in breast tumors with high miR-93 and miR-106a expression.

Conclusions:

  • A novel mechanism linking microRNAs and ubiquitination machinery in regulating cancer cell invasion has been identified.
  • The interplay between miR-93, miR-106a, FBXO31, and Slug contributes to maintaining an invasive cancer phenotype.
  • Targeting this microRNA-ubiquitination axis could offer new therapeutic strategies for invasive cancers.

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