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Aberrant expression of select piRNA-pathway genes does not reactivate piRNA silencing in cancer cells

Pavol Genzor1, Seth C Cordts1, Neha V Bokil1

  • 1National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.

Proceedings of the National Academy of Sciences of the United States of America
|May 22, 2019
PubMed

Insights

Cancer/testis genes, like those in the PIWI-interacting RNA (piRNA) pathway, are promising targets. However, this study found that while piRNA pathway genes are expressed in cancer, functional silencing complexes do not form, limiting their therapeutic potential.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Genetics

Background:

  • Germline genes aberrantly expressed in cancer cells offer therapeutic and diagnostic potential due to restricted physiological expression and immunogenicity.
  • Cancer/testis genes, particularly components of the PIWI-interacting small RNA (piRNA) pathway, are of interest for their role in controlling mobile genetic elements and potential to counteract cancer genome instability.

Purpose of the Study:

  • To systematically investigate the reactivation of functional piRNA-silencing mechanisms in the aberrant context of cancer.
  • To determine if PIWI protein expression alone impacts the cancer cell transcriptome.

Main Methods:

  • Systematic investigation of piRNA-pathway gene expression in cancer cells.
  • Analysis of piRNA-silencing complex formation.
  • Assessment of the impact of PIWI protein expression on the cancer cell transcriptome.

Main Results:

  • Individual piRNA-pathway genes are expressed in various cancer types.
  • Functional piRNA-silencing complexes were not detected in cancer cells.
  • Expression of a PIWI protein alone did not significantly alter the cancer cell transcriptome.

Conclusions:

  • Reactivation of piRNA silencing is not a prevalent phenomenon in cancer cells, despite the expression of individual pathway genes.
  • The aberrant expression of germline genes in cancer does not necessarily restore full functionality of associated regulatory pathways like piRNA silencing.
Keywords:
RNAcancergermlinepiRNAtransposon

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