The long non-coding RNAGHSROSreprograms prostate cancer cell lines toward a more aggressive phenotype

Abstract

ABSTRACTIt is now appreciated that long non-coding RNAs (lncRNAs) are important players in the orchestration of cancer progression. In this study we characterizedGHSROS, 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. Consistently, transcriptome data revealed thatGHSROSalters the expression of cancer-associated genes. Functional analysesin vitroshowed thatGHSROSmediates tumor growth, migration, and survival and resistance to the cytotoxic drug docetaxel. Increased cellular proliferation ofGHSROS-overexpressing PC3, DU145, and LNCaP prostate cancer cell linesin vitrowas recapitulated in a subcutaneous xenograft model. Conversely,in vitroantisense oligonucleotide inhibition of the lncRNA reciprocally regulated cell growth and migration, and gene expression. Notably,GHSROSmodulates 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 thatGHSROScan reprogram prostate cancer cells toward a more aggressive phenotype and that this lncRNA may represent a potential therapeutic target.