G protein-coupled receptor GPR160 is associated with apoptosis and cell cycle arrest of prostate cancer cells

// Caihong Zhou 1 , Xinchuan Dai 1 , Yi Chen 2 , Yanyan Shen 2 , Saifei Lei 1 , Ting Xiao 1 , Tamas Bartfai 3 , Jian Ding 2 , Ming-Wei Wang 1, 4 1 The National Center for Drug Screening and The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai 201203, China 2 The State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai 201203, China 3 Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA 4 School of Pharmacy, Fudan University, Shanghai 201203, China Correspondence to: Ming-Wei Wang, e-mail: mwwang@simm.ac.cn Keywords: GPR160, prostate cancer, orphan G protein-coupled receptor, cell cycle arrest, apoptosis Received: July 05, 2015      Accepted: January 26, 2016      Published: February 10, 2016 ABSTRACT G protein-coupled receptors (GPCRs) represent the largest membrane protein family implicated in the therapeutic intervention of a variety of diseases including cancer. Exploration of biological actions of orphan GPCRs may lead to the identification of new targets for drug discovery. This study investigates potential roles of GPR160, an orphan GPCR, in the pathogenesis of prostate cancer. The transcription levels of GPR160 in the prostate cancer tissue samples and cell lines, such as PC-3, LNCaP, DU145 and 22Rv1 cells, were significantly higher than that seen in normal prostate tissue and cells. Knockdown of GPR160 by lentivirus-mediated short hairpin RNA constructs targeting human GPR160 gene (ShGPR160) resulted in prostate cancer cell apoptosis and growth arrest both in vitro and in athymic mice. Differential gene expression patterns in PC-3 cells infected with ShGPR160 or scramble lentivirus showed that 815 genes were activated and 1193 repressed. Functional annotation of differentially expressed genes (DEGs) revealed that microtubule cytoskeleton, cytokine activity, cell cycle phase and mitosis are the most evident functions enriched by the repressed genes, while regulation of programmed cell death, apoptosis and chemotaxis are enriched significantly by the activated genes. Treatment of cells with GPR160 -targeting shRNA lentiviruses or duplex siRNA oligos increased the transcription of IL6 and CASP1 gene significantly. Our data suggest that the expression level of endogenous GPR160 is associated with the pathogenesis of prostate cancer.