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ADAR1 Transcriptome editing promotes breast cancer progression through the regulation of cell cycle and DNA damage

Eduardo A Sagredo1, Alfredo I Sagredo1, Alejandro Blanco2

  • 1Center of Excellence in Precision Medicine, Pfizer Chile, Obispo Arturo Espinoza Campos 2526, CP 7810305 Santiago, Chile; Centro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.

Biochimica Et Biophysica Acta. Molecular Cell Research
|April 11, 2020
PubMed

Insights

The double stranded RNA-specific adenosine deaminase (ADAR) enzyme impacts breast cancer progression by regulating genes involved in DNA damage response and cell proliferation. Reduced ADAR levels decrease cancer cell viability and increase apoptosis.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • RNA editing is a key mechanism in cancer progression.
  • ADAR enzymes regulate genes crucial for cell cycle, DNA damage response (DDR), and transcription.
  • The specific role of ADAR in breast cancer DDR and proliferation remains under-investigated.

Purpose of the Study:

  • To investigate the role of ADAR in breast cancer progression.
  • To determine the correlation between ADAR expression, clinical outcomes, and key gene pathways in breast cancer patients.
  • To elucidate ADAR's impact on mRNA stability, cell viability, and DDR activation in breast cancer cells.

Main Methods:

  • Correlation analysis of ADAR expression with clinical data and mRNA levels of edited transcripts.
  • ADAR knockdown experiments in breast cancer cell lines.
  • Assessment of mRNA stability, cell viability, apoptosis, and DDR activation.

Main Results:

  • ADAR expression significantly correlates with clinical outcomes and mRNA levels of DDR, cell cycle, and proliferation genes in breast cancer.
  • ADAR knockdown alters mRNA stability of DDR and DNA replication genes.
  • Reduced ADAR levels in breast cancer cells lead to decreased viability, increased apoptosis, and diminished DDR activation.

Conclusions:

  • ADAR plays a significant role in breast cancer progression.
  • ADAR regulates mRNA stability and expression of proliferation and DDR genes.
  • ADAR impacts breast cancer cell viability through modulation of DDR pathways.
Keywords:
Breast cancerDNA damage responseProliferationRNA editingRNA stability

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