PeerJ (2021-02-01)

The long non-coding RNA GHSROS reprograms prostate cancer cell lines toward a more aggressive phenotype

  • Patrick B. Thomas,
  • Penny Jeffery,
  • Manuel D. Gahete,
  • Eliza Whiteside,
  • Carina Walpole,
  • Michelle Maugham,
  • Lidija Jovanovic,
  • Jennifer Gunter,
  • Elizabeth Williams,
  • Colleen Nelson,
  • Adrian Herington,
  • Raul M. Luque,
  • Rakesh Veedu,
  • Lisa K. Chopin,
  • Inge Seim

DOI
https://doi.org/10.7717/peerj.10280
Journal volume & issue
Vol. 9
p. e10280

Abstract

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It is now appreciated that long non-coding RNAs (lncRNAs) are important players in orchestrating cancer progression. In this study we characterized GHSROS, a human lncRNA gene on the opposite DNA strand (antisense) to the ghrelin receptor gene, in prostate cancer. The lncRNA was upregulated by prostate tumors from different clinical datasets. Transcriptome data revealed that GHSROS alters the expression of cancer-associated genes. Functional analyses in vitro showed that GHSROS mediates tumor growth, migration and survival, and resistance to the cytotoxic drug docetaxel. Increased cellular proliferation of GHSROS-overexpressing PC3, DU145, and LNCaP prostate cancer cell lines in vitro was recapitulated in a subcutaneous xenograft model. Conversely, in vitro antisense oligonucleotide inhibition of the lncRNA reciprocally regulated cell growth and migration, and gene expression. Notably, GHSROS modulates the expression of PPP2R2C, the loss of which may drive androgen receptor pathway-independent prostate tumor progression in a subset of prostate cancers. Collectively, our findings suggest that GHSROS can reprogram prostate cancer cells toward a more aggressive phenotype and that this lncRNA may represent a potential therapeutic target.

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