Let-7b-5p sensitizes breast cancer cells to doxorubicin through Aurora Kinase B

Murat Kaya1, Asmaa Abuaisha2, Ilknur Suer3

  • 1Istanbul Faculty of Medicine, Department of Internal Medicine, Division of Medical Genetics, Istanbul University, Capa, Fatih, Istanbul, Turkey.

Plos One
|January 9, 2025
PubMed

Insights

MicroRNAs (miRNAs) like let-7b-5p are downregulated in breast cancer (BC), promoting Doxorubicin resistance by upregulating Aurora Kinase B (AURKB). Restoring let-7b-5p may overcome this resistance.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression.
  • Aberrant miRNA expression is implicated in breast cancer (BC) progression and drug resistance.
  • Doxorubicin (Dox) resistance is a major challenge in BC treatment.

Purpose of the Study:

  • To investigate the role of let-7b-5p in Doxorubicin resistance in breast cancer.
  • To explore the relationship between let-7b-5p, Aurora Kinase B (AURKB), and Doxorubicin resistance.
  • To determine the therapeutic potential of targeting the let-7b-5p/AURKB axis.

Main Methods:

  • Bioinformatic analysis of miRNA expression and gene correlation using public datasets (GEO).
  • Quantitative PCR (qPCR) to validate miRNA and gene expression in BC tissues.
  • Functional studies in breast cancer cell lines (MCF-10A, MCF-7, MDA-MB-231) to assess let-7b-5p effects on cell viability and Dox sensitivity via AURKB.

Main Results:

  • let-7b-5p was significantly downregulated in breast cancer tissues.
  • AURKB was identified as a key target gene negatively correlated with let-7b-5p and associated with Doxorubicin resistance.
  • let-7b-5p restoration inhibited cancer cell growth and sensitized cells to Doxorubicin by downregulating AURKB.

Conclusions:

  • The let-7b-5p/AURKB axis plays a critical role in breast cancer progression.
  • Disruption of this axis contributes to Doxorubicin resistance.
  • Targeting the let-7b-5p/AURKB pathway presents a potential strategy to overcome Doxorubicin resistance in breast cancer.

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