Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

The long non-coding RNA, GHSROS, mediates prostate cancer growth (#191)

Patrick Thomas 1 2 3 , Carina Maree Walpole 1 , Penny Jeffery 1 2 3 , Lidija Jovanovic 2 , Adrian Herington 1 2 , Colleen Nelson 2 , Eliza Whiteside 4 , Rakesh Veedu 5 , Inge Seim 1 2 3 , Lisa Chopin 1 2 3
  1. Ghrelin Research Group, Translational Research Institute/ Institute of Health and Biomedical Innovation - Queensland University of Technology, Brisbane, Queensland, Australia
  2. Australian Prostate Cancer Research Centre-Queensland, Queensland University of Technology (QUT)/ Princess Alexandra Hospital, Brisbane, Queensland, Australia
  3. Comparative and Endocrine Biology Laboratory, Translational Research Institute/ Institute of Health and Biomedical Innovation - Queensland University of Technology, Brisbane, Queensland, Australia
  4. Centre for Health Research, University of Southern Queensland, Toowoomba, Queensland, Australia
  5. Center for Comparative Genomics, Murdoch University/ Western Australian Neurosciences Research Institute, Perth, Western Australia, Australia

Long non-coding RNAs (lncRNAs) play key regulatory roles in cancer progression and are novel therapeutic targets1. We have discovered a lncRNA on the antisense strand of the ghrelin receptor gene (GHSR), termed GHSROS (GHSR opposite strand). Using quantitative RT-PCR we demonstrated that GHSROS is highly expressed in a subset of high grade prostate cancers. GHSROS over-expression significantly increased cell proliferation in the PC3 (1.76 ± 0.18 fold, P<0.01) and DU145 prostate cancer cell lines compared to vector control (1.74 fold ± 0.73 P<0.01), using xCELLigence real time cell analysis. GHSROS also increased cell migration in these cell lines compared to vector control (1.54 ± 0.35 fold in the PC3 cell line, P<0.05, and 1.94 ± 0.43 fold in the DU145 cell line, P<0.01). RNA sequencing in the PC3-GHSROS cell line demonstrated that genes associated with a metastatic prostate cancer gene signature were suppressed or induced by GHSROS. Using novel locked nucleic acid antisense oligonucleotides designed to target GHSROS, GHSROS silencing inhibited cell proliferation (-1.14 ± 0.07 fold, P<0.05) and migration (-1.9 ± 0.14 fold, P<0.05) in the PC3 cell line. Tumour growth was investigated in vivo using a subcutaneous NOD/SCID mouse xenograft model. Tumour volume was significantly increased in the PC3 and DU145 cell line xenografts over-expressing GHSROS (P<0.05). GHSROS may have clinical significance in prostate cancer as it is highly expressed in a significant subset of prostate cancers and is associated with a metastatic gene signature. GHSROS plays a role in cell proliferation, migration and tumour growth and may provide a useful target for the development of novel antisense therapies for prostate cancer treatment.

[1] Gutschner, T. and S. Diederichs. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol, 2012. 9(6): p. 703-19.