Glucose-based regulation of miR-451/AMPK signaling depends on the OCT1 transcription factor

Cell Rep. 2015 May 12;11(6):902-909. doi: 10.1016/j.celrep.2015.04.016. Epub 2015 Apr 30.


In aggressive, rapidly growing solid tumors such as glioblastoma multiforme (GBM), cancer cells face frequent dynamic changes in their microenvironment, including the availability of glucose and other nutrients. These challenges require that tumor cells have the ability to adapt in order to survive periods of nutrient/energy starvation. We have identified a reciprocal negative feedback loop mechanism in which the levels of microRNA-451 (miR-451) are negatively regulated through the phosphorylation and inactivation of its direct transcriptional activator OCT1 by 5' AMP-activated protein kinase (AMPK), which is activated by glucose depletion-induced metabolic stress. Conversely, in a glucose-rich environment, unrestrained expression of miR-451 suppresses AMPK pathway activity. These findings uncover miR-451 as a major effector of glucose-regulated AMPK signaling, allowing tumor cell adaptation to variations in nutrient availability in the tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3T3 Cells
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Gene Expression Regulation
  • Glucose / pharmacology*
  • Humans
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Octamer Transcription Factor-1 / metabolism*
  • Phosphorylation / drug effects
  • Promoter Regions, Genetic / genetics
  • Signal Transduction / drug effects*
  • Transcription, Genetic / drug effects


  • MIRN451 microRNA, human
  • MicroRNAs
  • Mirn451 microRNA, mouse
  • Octamer Transcription Factor-1
  • AMP-Activated Protein Kinases
  • Glucose