title: Upregulation of PAWR by small activating RNAs induces cell apoptosis in human prostate cancer cells.
abstract: RNA activation (RNAa) is a promising discovery whereby expression of a particular gene can be induced by targeting its promoter using small double-stranded RNAs (dsRNAs) also termed small activating RNAs (saRNAs). We previously reported that several small dsRNAs targeting the PRKC apoptosis WT1 regulator (PAWR) promoter can upregulate PAWR gene expression effectively in human cancer cells. The present study was conducted to evaluate the antitumor potential of PAWR gene induction by these saRNAs in prostate cancer cells. Promisingly, we found that upregulation of PAWR by saRNA inhibited the growth of prostate cancer cells by inducing cell apoptosis which was related to inactivation of the NF-κB and Akt pathways. The decreased anti‑apoptotic protein Bcl-2 and activation of the caspase cascade and poly(ADP-ribose) polymerase (PARP) also supported the efficacy of the treatment. Overall, these data suggest that activation of PAWR by saRNA may have a therapeutic benefit for prostate and other types of cancer.
authors.affiliation: Department of Urology, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Traditional Chinese Medical Hospital of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Urology, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Shan-Wen
authors.initials: SW
authors.lastname: Chen
authors.affiliation: Department of Urology, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Urology, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Xiang-Yi
authors.initials: XY
authors.lastname: Zheng
authors.affiliation: Department of Urology, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Xie
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D012330:RNA, Double-Stranded; C101296:prostate apoptosis response-4 protein