PLoS ONE (Jan 2012)

A daphnane diterpenoid isolated from Wikstroemia polyantha induces an inflammatory response and modulates miRNA activity.

  • Anthony Khong,
  • Roberto Forestieri,
  • David E Williams,
  • Brian O Patrick,
  • Andrea Olmstead,
  • Victoria Svinti,
  • Emily Schaeffer,
  • François Jean,
  • Michel Roberge,
  • Raymond J Andersen,
  • Eric Jan

DOI
https://doi.org/10.1371/journal.pone.0039621
Journal volume & issue
Vol. 7, no. 6
p. e39621

Abstract

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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.