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Cell Physiol Biochem. 2018;51(4):1932-1944. doi: 10.1159/000495718. Epub 2018 Dec 4.

microRNA-15 Activates NF-κB Pathway via Down Regulating Expression of Adenosine A2 Receptor in Ulcerative Colitis.

Author information

1
Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Chinahuixiazhang1@hotmail.com.
2
Department of Physiology and neurobiology, School of Basic Medicine Sciences, Zhengzhou University, Zhengzhou, China.

Abstract

BACKGROUND/AIMS:

The role of miR-15 in ulcerative colitis (UC) is unclear. In this study, we found that miR-15 downregulated the expression of adenosine A2a receptor (A2aAR) in the colonic tissues of patients with UC and in HT-29 human colonic epithelial cells.

METHODS:

The study population comprised patients with UC (n=23), irritable bowel syndrome (IBS, n=22), and healthy subjects (n = 20). The levels of miR-15, A2aAR, and protein in colon tissue biopsies were determined by real-time quantitative reverse transcription polymerase chain reaction, immunofluorescence staining, and Western blotting. The TargetScan prediction algorithm was used to identify the miR-15 binding site in the 3'-UTR of A2aAR. To assess the effects of miR-15 on A2aAR levels, HT-29 cells were transfected with miR-15 mimics.

RESULTS:

Relative to expression in healthy subjects, A2aAR expression was decreased in UC patients and was similar in IBS patients. MiR-15 levels were higher in UC patients than in IBS patients or healthy subjects. A2aAR was the target of miR-15 in HT-29 cells, which downregulated A2aAR mRNA levels. MiR-15 mimics induced nuclear translocation of NF-κB p65 and upregulated the expression of IL-8 and IFN-γ in colonic epithelial cells; these effects were reversed by an miR-15 inhibitor. A2aAR knockdown confirmed that miR-15 activated the NF-κB cascade.

CONCLUSION:

Our data suggest that miR-15 modulates inflammatory and immune responses by suppressing the expression of A2aAR and regulating the NF-κB cascade.

KEYWORDS:

A2aAR; NF-κB; Ulcerative colitis; miRNA-15

PMID:
30513523
DOI:
10.1159/000495718
[Indexed for MEDLINE]
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