MicroRNA-7 mediates cross-talk between metabolic signaling pathways in the liver

Sci Rep. 2018 Jan 10;8(1):361. doi: 10.1038/s41598-017-18529-x.

Abstract

MicroRNAs (miRNAs) have emerged as critical regulators of cellular metabolism. To characterise miRNAs crucial to the maintenance of hepatic lipid homeostasis, we examined the overlap between the miRNA signature associated with inhibition of peroxisome proliferator activated receptor-α (PPAR-α) signaling, a pathway regulating fatty acid metabolism, and the miRNA profile associated with 25-hydroxycholesterol treatment, an oxysterol regulator of sterol regulatory element binding protein (SREBP) and liver X receptor (LXR) signaling. Using this strategy, we identified microRNA-7 (miR-7) as a PPAR-α regulated miRNA, which activates SREBP signaling and promotes hepatocellular lipid accumulation. This is mediated, in part, by suppression of the negative regulator of SREBP signaling: ERLIN2. miR-7 also regulates genes associated with PPAR signaling and sterol metabolism, including liver X receptor β (LXR-β), a transcriptional regulator of sterol synthesis, efflux, and excretion. Collectively, our findings highlight miR-7 as a novel mediator of cross-talk between PPAR, SREBP, and LXR signaling pathways in the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Energy Metabolism / drug effects
  • Energy Metabolism / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Hepatitis C / genetics
  • Hepatitis C / metabolism
  • Hepatitis C / virology
  • Hepatocytes / metabolism
  • Humans
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics
  • Liver / metabolism*
  • Liver / virology
  • Metabolic Networks and Pathways* / drug effects
  • MicroRNAs / genetics*
  • PPAR alpha / antagonists & inhibitors
  • PPAR alpha / metabolism
  • Signal Transduction* / drug effects
  • Sterol Regulatory Element Binding Proteins / metabolism

Substances

  • MIRN7 microRNA, human
  • MicroRNAs
  • PPAR alpha
  • Sterol Regulatory Element Binding Proteins

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