title: A daphnane diterpenoid isolated from Wikstroemia polyantha induces an inflammatory response and modulates miRNA activity.
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 3'untranslated region (3'UTR) 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 development of the cell-based miRNA sensor system should prove useful in identifying compounds that affect miRNA/siRNA activity.
authors: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Anthony
authors: A
authors: Khong
authors: Roberto
authors: R
authors: Forestieri
authors: David E
authors: DE
authors: Williams
authors: Brian O
authors: BO
authors: Patrick
authors: Andrea
authors: A
authors: Olmstead
authors: Victoria
authors: V
authors: Svinti
authors: Emily
authors: E
authors: Schaeffer
authors: François
authors: F
authors: Jean
authors: Michel
authors: M
authors: Roberge
authors: Raymond J
authors: RJ
authors: Andersen
authors: Eric
authors: E
authors: Jan
mesh_terms: D020413:3' Untranslated Regions; D002460:Cell Line; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D006526:Hepatitis C / Q000517:prevention & control; D007249:Inflammation / Q000139:chemically induced*; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D032365:Wikstroemia / Q000737:chemistry*
chemical_list: D020413:3' Untranslated Regions; D004224:Diterpenes; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha