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
Affiliations
Patrick B. Thomas
Ghrelin Research Group, Translational Research Institute, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
Penny Jeffery
Ghrelin Research Group, Translational Research Institute, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
Manuel D. Gahete
Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
Eliza Whiteside
Centre for Health Research, University of Southern Queensland, Toowoomba, Queensland, Australia
Carina Walpole
Ghrelin Research Group, Translational Research Institute, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
Michelle Maugham
Ghrelin Research Group, Translational Research Institute, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
Lidija Jovanovic
Australian Prostate Cancer Research Centre - Queensland, Queensland University of Technology, Brisbane, Queensland, Australia
Jennifer Gunter
Australian Prostate Cancer Research Centre - Queensland, Queensland University of Technology, Brisbane, Queensland, Australia
Elizabeth Williams
Australian Prostate Cancer Research Centre - Queensland, Queensland University of Technology, Brisbane, Queensland, Australia
Colleen Nelson
Australian Prostate Cancer Research Centre - Queensland, Queensland University of Technology, Brisbane, Queensland, Australia
Adrian Herington
Ghrelin Research Group, Translational Research Institute, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
Raul M. Luque
Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
Rakesh Veedu
Centre for Comparative Genomics, Murdoch University, Perth, Western Australia, Australia
Lisa K. Chopin
Ghrelin Research Group, Translational Research Institute, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
Inge Seim
Ghrelin Research Group, Translational Research Institute, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
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.
