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Regeneration linked miRNA modify tumor phenotype and can enforce multi-lineage growth arrest in vivo

Siamak Salehi1, Oliver D Tavabie1, Augusto Villanueva1

  • 1Institute of Liver Studies, King's College Hospital, London, SE5 9RS, UK.

Scientific Reports
|May 19, 2021
PubMed

Insights

MicroRNAs (miRNAs) regulating liver regeneration also impact cancer growth. Inhibiting specific miRNAs can enhance tumor proliferation, while others can halt cancer growth, suggesting novel miRNA-based cancer therapies.

Area of Science:

  • Molecular Biology
  • Oncology
  • Regenerative Medicine

Background:

  • Cell proliferation is crucial for regeneration but dysregulated in cancer.
  • MicroRNAs (miRNAs) have been identified as regulators of human liver regeneration.
  • The role of these regenerative miRNAs in modulating tumor behavior is unexplored.

Purpose of the Study:

  • To investigate if miRNAs regulating liver regeneration directly influence cancer behavior.
  • To determine the effect of specific miRNA inhibition on tumor proliferation and aggressiveness.
  • To explore the potential of miRNA-based strategies for cancer treatment.

Main Methods:

  • In vitro and in vivo experiments using cancer models.
  • Inhibition and enforced expression of specific miRNAs (-503, -23a, -152).
  • Assessment of tumor proliferation, gene expression, and methylation patterns.

Main Results:

  • Inhibition of miRNAs -503 and -23a promoted tumor proliferation and aggressiveness in vitro and in vivo.
  • Inhibition of miRNA-152 induced DNMT1, leading to methylation, altered gene expression, and growth inhibition.
  • Modulating miRNA expression to mimic failed regeneration halted multi-lineage cancer growth in vivo.

Conclusions:

  • Regulation of regeneration and tumor aggressiveness are linked.
  • miRNA-based inhibitors targeting regeneration pathways show promise as a novel cancer treatment strategy.

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