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.
 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.