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Inverse Impact of Cancer Drugs on Circular and Linear RNAs in Breast Cancer Cell Lines

Anna Terrazzan1,2, Francesca Crudele3, Fabio Corrà1

  • 1Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy.

Non-Coding RNA
|May 23, 2023
PubMed

Insights

Anticancer drugs alter circular RNA (circRNA) and linear RNA (linRNA) expression in breast cancer cells, changing their ratios. Some drug-regulated circRNAs promote cancer, while others may indicate drug response.

Area of Science:

  • Molecular Biology
  • Genomics
  • Cancer Research

Background:

  • Altered circular RNA (circRNA) expression is implicated in breast cancer.
  • The impact of anticancer drugs on circRNA and cognate linear RNA (linRNA) regulation remains largely unknown.

Purpose of the Study:

  • To investigate the effects of various anticancer agents on the expression of 12 cancer-related circRNAs and their linRNAs in breast cancer cell lines.
  • To determine the relationship between circRNA/linRNA expression ratios and drug treatment.
  • To identify drug-regulated circRNAs with potential oncogenic or anticancer roles.

Main Methods:

  • Analysis of 12 cancer-related circRNAs and their linRNAs in two breast cancer cell lines (MCF-7 and MDA-MB-231).
  • Treatment of cell lines with 14 different anticancer agents targeting various cellular pathways.
  • Quantification of circRNA and linRNA expression levels and calculation of their ratios.

Main Results:

  • Drug exposure led to increased circRNA/linRNA expression ratios, primarily due to linRNA downregulation and circRNA upregulation.
  • Specific circRNAs like circ/linVRK1 and circ/linMAN1A2 showed differential regulation by drugs, with opposing effects on apoptosis and cell migration.
  • Some circRNAs, such as circ/linHIPK3, correlated with pathways involved in cancer progression and drug resistance (e.g., PI3K/AKT pathway).
  • Certain drug treatments (AMG511, GSK1070916) decreased circGFRA1 in MDA-MB-231 cells, suggesting a positive drug response.

Conclusions:

  • Anticancer drugs significantly alter circRNA and linRNA expression patterns in breast cancer cells.
  • Drug-regulated circRNAs can have distinct roles, either promoting or inhibiting cancer progression.
  • circRNA/linRNA profiles may serve as biomarkers for drug response and cancer progression, potentially linked to specific mutated pathways.
Keywords:
breast cancercircular RNAdrugs

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