miR-24 regulates menin in the endocrine pancreas

Am J Physiol Endocrinol Metab. 2014 Jul 1;307(1):E84-92. doi: 10.1152/ajpendo.00542.2013. Epub 2014 May 13.

Abstract

Menin, the product of the MEN1 gene, functions as a tumor suppressor and was first identified in 1997 due to its causative role in the endocrine tumor disorder multiple endocrine neoplasia, type 1 (MEN1). More recently, menin has been identified as a key player in pancreatic islet biology with the observation of an inverse relationship between menin levels and pancreatic islet proliferation. However, the factors regulating menin and the MEN1 gene in the pancreas are poorly understood. Here, we describe the regulation of menin by miR-24 and demonstrate that miR-24 directly decreases menin levels and impacts downstream cell cycle inhibitors in MIN6 insulinoma cells and in βlox5 immortalized β-cells. This regulation of menin impacts cell viability and proliferation in βlox5 cells. Furthermore, our data show a feedback regulation between miR-24 and menin that is present in the pancreas, suggesting that miR-24 regulates menin levels in the pancreatic islet.

Keywords: MEN1; menin; miR-24; miRNA; pancreatic islet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cell Survival
  • Cells, Cultured
  • Gene Expression Regulation / physiology*
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / physiopathology*
  • Mice
  • Mice, Knockout
  • MicroRNAs / physiology*
  • Pancreas / metabolism*
  • Proto-Oncogene Proteins / physiology*

Substances

  • Men1 protein, mouse
  • MicroRNAs
  • Mirn24 microRNA, mouse
  • Proto-Oncogene Proteins