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Aurora kinase A regulates cancer-associated RNA aberrant splicing in breast cancer

Sisi Li1,2, Yangfan Qi2, Jiachuan Yu3

  • 1Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.

Heliyon
|July 7, 2023
PubMed

Insights

Oncogenic Aurora kinase A (AURKA) drives aberrant RNA splicing in breast cancer by interacting with splicing factors. Targeting nuclear AURKA offers a potential therapeutic strategy for breast cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Oncogenes significantly influence tumor-associated RNA splicing, but mechanisms require further elucidation.
  • Aurora kinase A (AURKA) is an oncogene implicated in various cancers, including breast cancer.

Purpose of the Study:

  • To investigate the role of oncogenic Aurora kinase A (AURKA) in regulating aberrant RNA splicing in breast cancer.
  • To elucidate the molecular mechanisms by which AURKA modulates RNA splicing and its clinical relevance.

Main Methods:

  • Analysis of RNA splicing events regulated by AURKA in breast cancer.
  • Investigation of AURKA interactions with splicing factors YBX1 and hnRNPK.
  • Assessment of clinical data linking AURKA complexes to patient prognosis.
  • Evaluation of small molecule inhibitors targeting AURKA nuclear translocation.

Main Results:

  • AURKA regulates pan-breast cancer-associated splicing events, including GOLGA4 and RBM4, which are linked to cancer development.
  • AURKA interacts with YBX1 to promote GOLGA4 exon inclusion and with hnRNPK to mediate RBM4 exon skipping.
  • Clinical data reveal an association between AURKA-YBX1/hnRNPK complexes and poor breast cancer prognosis.
  • Inhibition of AURKA nuclear translocation partially reverses aberrant splicing of GOLGA4 and RBM4 in breast cancer cells.

Conclusions:

  • Oncogenic AURKA plays a crucial role in modulating breast cancer-associated RNA splicing.
  • Nuclear AURKA is identified as a potential therapeutic target for breast cancer treatment.
Keywords:
Aurora kinase ABreast cancerRNA splicingSplicing factor

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