Recurrent fusion RNA DUS4L-BCAP29 in non-cancer human tissues and cells

Oncotarget. 2017 May 9;8(19):31415-31423. doi: 10.18632/oncotarget.16329.

Abstract

Traditional gene fusions are involved in the development of various neoplasia. DUS4L-BCAP29, a chimeric fusion RNA, has been reported to be a cancer-fusion in prostate and gastric cancer, in addition to playing a tumorigenic role. Here, we showed that the DUS4L-BCAP29 fusion transcript exists in a variety of normal tissues. It is also present in non-cancer epithelial, as well as in fibroblast cell lines. Quantitatively, the fusion transcript has a comparable expression in non-cancerous, gastric and prostate cell lines and tissues as in the cancer cell lines and tissues. The loss-of-function approach as previously reported is not sufficient to prove the functionality of the fusion. On the other hand, the gain-of-function approach showed that overexpression of DUS4L-BCAP29 promotes cell growth and motility, even in non-cancer cells. Finally, we provide further evidence that the fusion transcript is a product of cis-splicing between adjacent genes. In summary, we believe that in contrast to traditional gene fusions, DUS4L-BCAP29 cannot be used as a cancer biomarker. Instead, it is a fusion transcript that exists in normal physiology and that its pro-growth effect is not unique to cancer cells.

Keywords: DUS4L-BCAP29; chimeric RNA; cis-SAGe; fusion transcript.

MeSH terms

  • Cell Line
  • Cell Line, Tumor
  • Gain of Function Mutation
  • Gene Expression
  • Gene Fusion*
  • Humans
  • Loss of Function Mutation
  • Male
  • Membrane Proteins / genetics*
  • Organ Specificity / genetics
  • Prostatic Neoplasms / genetics
  • RNA*
  • Sequence Analysis, DNA
  • Stomach Neoplasms / genetics
  • Transcription, Genetic

Substances

  • BCAP29 protein, human
  • Membrane Proteins
  • RNA