Role of miR-19a targeting TNF-α in mediating ulcerative colitis

Scand J Gastroenterol. 2013 Jul;48(7):815-24. doi: 10.3109/00365521.2013.800991.

Abstract

Objective: Ulcerative colitis (UC) is a widely studied inflammatory disease associated with differential expression of genes involved in immune function, wound healing, and tissue remodeling. MicroRNAs have been reported to play a role in various cancer types. However, the mechanism of how microRNAs regulate UC remains unclear.

Methods: In the present study, we investigated the role of miR-19a and tumor necrosis factor (TNF)-α in human colon tissues with UC and dextran sodium sulfate (DSS)-induced experimental colitis.

Results: We identified that the expression of miR-19a was significantly reduced and TNF-α was remarkably increased in human colon tissue with UC. Moreover, this observation of miR-19a and TNF-α was also occurred in DSS-treated mice colitis. Further, we observed that miR-19a directly regulated TNF-α expression because miR-19a can suppress the expression of wild-type TNF-α reporter, but not the mutant form. The expression of inflammatory factors TNF-α, IL-8, and GM-GSF were significantly elevated upon application of miR-19a inhibitor.

Conclusion: Taken together, this study determines the levels of miR-19a and TNF-α in both DSS-induced experimental murine colitis and human UC and further demonstrates that miR-19a might directly regulate TNF-α. The findings may provide a new insight in the clinical treatment of UC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Biomarkers / metabolism
  • Blotting, Western
  • Case-Control Studies
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / genetics
  • Colitis, Ulcerative / metabolism*
  • Colon / metabolism*
  • Dextran Sulfate
  • Down-Regulation
  • Female
  • HT29 Cells
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Middle Aged
  • Real-Time Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / metabolism*
  • Up-Regulation

Substances

  • Biomarkers
  • MIRN19 microRNA, human
  • MIRN19 microRNA, mouse
  • MicroRNAs
  • Tumor Necrosis Factor-alpha
  • Dextran Sulfate