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

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.

Key Words::

• DSS
• inflammatory bowel disease
• miR-19a
• miRNA
• TNF-α
• ulcerative colitis

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81001506).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.