title: Promoter-targeted double-stranded small RNAs activate PAWR gene expression in human cancer cells.
abstract: RNA activation is a promising discovery that promoter-targeted double-stranded small RNAs, termed small activating RNAs (saRNAs), can induce gene expression, which represents a novel approach to gene over-expression without traditional vector-based systems. PAWR is a tumor suppressing gene essential for apoptosis and a cancer-selective target for cancer therapeutics. Here our study identified synthetic saRNAs that could activate the expression of PAWR in human cancer cells. Functional analysis of PAWR induction revealed that saRNA treatment induced growth inhibition and apoptosis of cancer cells, and predictably modulated the expression of known downstream target gene Bcl-2. New functional saRNAs can also be harvested by one or two-base shifting of the original target sites. Chromatin immunoprecipitation assays indicated that activation of PAWR is accompanied by reduced dimethylation at histone H3K9 and increased dimethylation at histone H3K4. Moreover, the existence of transcripts in PAWR promoter was detected but its relationship with RNA activation needs more lucubration. These data have enlarged the gene pool of RNAa and hold great promise as an alternative for PAWR-targeted therapeutics.
authors.affiliation: Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Yan-Qi
authors.initials: YQ
authors.lastname: Xie
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Lin
authors.forename: Jie
authors.initials: J
authors.lastname: Qin
authors.forename: Qi-Qi
authors.initials: QQ
authors.lastname: Mao
authors.forename: Xiang-Yi
authors.initials: XY
authors.lastname: Zheng
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Xie
mesh_terms: D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D015870:Gene Expression; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000235:genetics; D012342:RNA, Small Nuclear; D015533:Transcriptional Activation
chemical_list: D051017:Apoptosis Regulatory Proteins; D006657:Histones; D019253:Proto-Oncogene Proteins c-bcl-2; D012330:RNA, Double-Stranded; D012342:RNA, Small Nuclear; C101296:prostate apoptosis response-4 protein