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EPHA2 antisense RNA modulates EPHA2 mRNA levels in basal-like/triple-negative breast cancer cells

Tetsuya Okuyama1, Ryou Sakamoto2, Kazuhiro Kumagai2

  • 1Medical Chemistry Laboratory, Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Kusatsu, Shiga, 525-8577, Japan.

Biochimie
|October 6, 2020
PubMed

Insights

A natural antisense RNA (EPHA2-AS) regulates Ephrin type-A receptor 2 (EPHA2) mRNA levels. This long non-coding RNA is crucial for EPHA2 protein production, impacting triple-negative breast cancer tumorigenesis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Ephrin type-A receptor 2 (EPHA2) is a receptor tyrosine kinase (RTK) overexpressed in various cancers, including breast cancer.
  • EPHA2's role in tumorigenesis necessitates understanding its gene expression regulation.
  • Triple-negative breast cancer (TNBC) exhibits high EPHA2 levels.

Purpose of the Study:

  • To investigate the role of EPHA2 antisense RNA (EPHA2-AS) in regulating EPHA2 mRNA levels.
  • To determine the mechanism by which EPHA2-AS modulates EPHA2 expression.
  • To assess the significance of EPHA2-AS in breast cancer, particularly TNBC.

Main Methods:

  • Characterization of EPHA2-AS as a long non-coding RNA (lncRNA) with two splice variants (EPHA2-AS1/2).
  • Analysis of EPHA2-AS and EPHA2 mRNA expression in breast cancer cell lines and patient samples.
  • Experimental manipulation of EPHA2-AS levels using sense and antisense oligonucleotides.
  • Investigation of EPHA2-AS interaction with EPHA2 mRNA and microRNA response elements.

Main Results:

  • EPHA2-AS is constitutively expressed and concordant with EPHA2 mRNA, especially in TNBC.
  • EPHA2-AS1/2 directly modulates EPHA2 mRNA levels through interaction with a complementary region.
  • EPHA2-AS does not interfere with microRNA binding to shared response elements.
  • EPHA2-AS plays a critical role in regulating EPHA2 protein production.

Conclusions:

  • EPHA2-AS is a key regulator of EPHA2 mRNA and protein levels.
  • EPHA2-AS contributes to the oncogenesis of TNBC by modulating EPHA2 expression.
  • Understanding EPHA2-AS regulation offers potential therapeutic targets for breast cancer.
Keywords:
EPHA2EPHA2 antisense RNAMDA-MB-231 cellsNATTriple-negative breast cancerslncRNA

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