Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA

Cell Res. 2012 Jan;22(1):107-26. doi: 10.1038/cr.2011.158. Epub 2011 Sep 20.

Abstract

Our previous studies have demonstrated that stable microRNAs (miRNAs) in mammalian serum and plasma are actively secreted from tissues and cells and can serve as a novel class of biomarkers for diseases, and act as signaling molecules in intercellular communication. Here, we report the surprising finding that exogenous plant miRNAs are present in the sera and tissues of various animals and that these exogenous plant miRNAs are primarily acquired orally, through food intake. MIR168a is abundant in rice and is one of the most highly enriched exogenous plant miRNAs in the sera of Chinese subjects. Functional studies in vitro and in vivo demonstrated that MIR168a could bind to the human/mouse low-density lipoprotein receptor adapter protein 1 (LDLRAP1) mRNA, inhibit LDLRAP1 expression in liver, and consequently decrease LDL removal from mouse plasma. These findings demonstrate that exogenous plant miRNAs in food can regulate the expression of target genes in mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adult
  • Animals
  • Asian Continental Ancestry Group
  • Chromatin Immunoprecipitation
  • Computational Biology
  • Diet
  • Female
  • Gene Expression Regulation*
  • Hep G2 Cells
  • Herbivory
  • Humans
  • Liver / cytology
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / blood
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Oryza / genetics*
  • Plasmids / genetics
  • Plasmids / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Plant / blood
  • RNA, Plant / genetics
  • RNA, Plant / metabolism*
  • RNA, Untranslated
  • Secretory Vesicles / metabolism
  • Substrate Specificity
  • Transfection
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • LDLRAP1 protein, human
  • Ldlrap1 protein, mouse
  • MicroRNAs
  • RNA, Messenger
  • RNA, Plant
  • RNA, Untranslated