期刊
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
卷 45, 期 7, 页码 1338-1346出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2013.03.022
关键词
RNA activation; Small activating RNA; PAWR; Non-coding transcript; Histone modification
资金
- National Natural Science Foundation of China [81101718, 30973466]
- Zhejiang Provincial Natural Science Foundation of China [Z2090356]
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. (C) 2013 Elsevier Ltd. All rights reserved.
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