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

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.

MiR‐27 alleviates myocardial cell damage induced by hypoxia/reoxygenation via targeting TGFBR1 and inhibiting NF‐κB pathway

“…There is some evidence to demonstrate that cold inducible RNA‐binding protein preserved H9c2 cells from cardiomyocyte via inhibiting NF‐κB pathway . Many reports illustrated that many miRNAs have effects on NF‐κB pathway . According to Xing et al, miRNA‐183 could improve myocardial damage via NF‐κB signaling .…”

“…31 Many reports illustrated that many miRNAs have effects on NF-κB pathway. 32,33 According to Xing et al, miRNA-183 could improve myocardial damage via NF-κB signaling. 34 Thus far, previous study has confirmed that upregulation of miR-27 suppressed the pathogenesis of osteoarthritis by inactivating the NF-κB pathway.…”

Inflammatory Bowel Diseases: It's Time for the Adenosine System

“…Crohn's patients with active disease displayed an increased A 2A receptor mRNA expression in colonic mucosa, while no changes were observed in patients with ulcerative colitis (18). Conversely, others reported a decreased mRNA and protein expression of A 2A receptor in sigmoid colonic mucosa from active ulcerative colitis patients (19,20). In addition, the authors observed that A 2A receptor expression was oppositely related with miR-16 expression (19).…”

“…In particular, miR-16, targeting the 3 ′ -UTR of A 2A receptor mRNA, has been found to inhibit A 2A receptor transcription (19). Zhang et al (20) observed a correlation between the increase in miR-15 and a decreased expression of A 2A receptor mRNA in colonic tissues from ulcerative colitis patients. The authors demonstrated in HT-29 cell lines that miR-15 downregulated A 2A receptor mRNA expression, which, in turn, decreased the activation of pro-inflammatory NF-κB signaling (20).…”

miR‐922 regulates apoptosis, migration, and invasion by targeting SOCS1 in gastric cancer

“…In general, miRNAs play an inhibitory role in tumors and various diseases . However, some studies have shown that some miRNAs can promote the progress of cancers and a variety of other diseases . miR‐922 is considered to be a tumor‐promoting gene, which can promote the occurrence and progress of tumor.…”