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.