MicroRNA-127 inhibits cell proliferation via targeting Kif3b in pancreatic β cells

Aging (Albany NY). 2019 Mar 1;11(5):1342-1355. doi: 10.18632/aging.101835.

Abstract

MicroRNAs (miRNAs) have been implicated in β cells dysfunction. Previous studies indicated that miR-127 was specifically abundant in β cells and one of its target genes, Kif3b, promoted cell proliferation. However, the impact of the miR-127-Kif3b axis on β cells remains unknown. In this study, we revealed that miR-127 level was declined both in islets from the mice with a high-fat diet and in MIN6 cells with elevated glucose treatment. The elevated level of miR-127 attenuated β cell proliferation by repressing Kif3b expression without affecting apoptosis and cell cycle, and it dampened insulin secretion. Moreover, β cell-derived miR-127 could also affect the islet endothelial cell-line, MS1, in vitro via the transfer of extracellular vesicles (EVs). Treating MS1 cells with the EVs secreted by MIN6 cells exhibited a higher ability in cell migration and tube formation. However, this effect was abolished by the miR-127 inhibitor co-cultured with EVs-treated MS1 cells. Thus, we define that miR-127 is a crucial regulator of insulin secretion and cell proliferation in pancreatic β cells as well as a potential functional regulation factor in islet endothelial cells.

Keywords: EVs; cell viability; insulin secretion; miR-127; β cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Diet, High-Fat
  • Down-Regulation
  • Extracellular Vesicles / physiology
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Glucose / administration & dosage
  • Glucose / pharmacology
  • Insulin / metabolism
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism*
  • Kinesins
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*

Substances

  • Insulin
  • Kif3b protein, mouse
  • MicroRNAs
  • Mirn127 microRNA, mouse
  • Kinesins
  • Glucose