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Connexin43 pseudogene in breast cancer cells offers a novel therapeutic target

Andrew Bier1, Irene Oviedo-Landaverde, Jing Zhao

  • 1Department of Oncology, Segal Cancer Centre, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, and Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec, Canada H3T 1E2.

Molecular Cancer Therapeutics
|April 18, 2009
PubMed

Insights

A breast cancer pseudogene, PsiCx43, inhibits Connexin43 (Cx43) translation. Restoring Cx43 levels via PsiCx43 knockdown increases chemotherapy sensitivity, suggesting pseudogene regulation as a therapeutic target.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Connexin43 (Cx43) is frequently altered in breast cancer, and its reexpression inhibits tumor growth and enhances chemotherapy response.
  • Pseudogenes are DNA sequences resembling functional genes, often considered non-functional, but emerging evidence suggests roles in gene regulation.

Purpose of the Study:

  • To investigate the role of the Connexin43 pseudogene (PsiCx43) in breast cancer.
  • To determine if PsiCx43 influences Cx43 expression and affects cancer cell sensitivity to chemotherapy.

Main Methods:

  • Analysis of PsiCx43 transcription in breast cancer cell lines versus normal cells.
  • In vivo and in vitro studies to assess PsiCx43 translation and its interaction with the translational machinery.
  • Assessment of Cx43 RNA and protein levels following PsiCx43 knockdown.
  • Evaluation of breast cancer cell sensitivity to chemotherapy after PsiCx43 modulation.

Main Results:

  • The Cx43 pseudogene (PsiCx43) is transcribed exclusively in breast cancer cells and can be translated into a protein with growth-suppressive properties.
  • Exogenous expression of PsiCx43 inhibits Cx43 translation by binding to polyribosomes; PsiCx43 binds more efficiently than Cx43 in vitro.
  • Knockdown of PsiCx43 in breast cancer cells leads to increased Cx43 RNA and protein levels.
  • Reduced PsiCx43 expression enhances breast cancer cell sensitivity to cytotoxic chemotherapy.

Conclusions:

  • PsiCx43 functions as a posttranscriptional regulator of Cx43 in breast cancer.
  • This pseudogene-mediated regulation of Cx43 offers potential therapeutic strategies for breast cancer treatment.

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