a daphnane diterpenoid isolated from wikstroemia polyantha induces an inflammatory response and modulates mirna activity一个瑞香烷二萜隔绝wikstroemia polyantha诱发炎症反应和调节microrna的活动.pdfVIP

A Daphnane Diterpenoid Isolated from Wikstroemia polyantha Induces an Inflammatory Response and Modulates miRNA Activity 1 2 2 2 3 Anthony Khong , Roberto Forestieri , David E. Williams , Brian O. Patrick , Andrea Olmstead , 3 1 3 1 2 1 Victoria Svinti , Emily Schaeffer , Franc¸ois Jean , Michel Roberge , Raymond J. Andersen , Eric Jan * 1 Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada, 2 Department of Chemistry and Department of Earth and Ocean Sciences, University of British Columbia, Vancouver, British Columbia, Canada, 3 Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada Abstract MicroRNAs (miRNAs) are endogenously expressed single-stranded ,21–23 nucleotide RNAs that inhibit gene expression post-transcriptionally by binding imperfectly to elements usually within the 39untranslated region (39UTR) of mRNAs. Small interfering RNAs (siRNAs) mediate site-specific cleavage by binding with perfect complementarity to RNA. Here, a cell-based miRNA reporter system was developed to screen for compounds from marine and plant extracts that inhibit miRNA or siRNA activity. The daphnane diterpenoid genkwanine M (GENK) isolated from the plant Wikstroemia polyantha induces an early inflammatory response and can moderately inhibit miR-122 activity in the liver Huh-7 cell line. GENK does not alter miR-122 levels nor does it directly inhibit siRNA activity in an in vitro cleavage assay. Finally, we demonstrate that GENK can inhibit HCV infection in Huh-7 cells. In summary, the developm