title: MicroRNA-16 is putatively involved in the NF-κB pathway regulation in ulcerative colitis through adenosine A2a receptor (A2aAR) mRNA targeting.
abstract: MicroRNAs (miRNAs) act as important post-transcriptional regulators of gene expression by targeting the 3'-untranslated region of their target genes. Altered expression of miR-16 is reported in human ulcerative colitis (UC), but its role in the development of the disease remains unclear. Adenosine through adenosine A2a receptor (A2aAR) could inhibit nuclear factor-kappaB (NF-κB) signaling pathway in inflammation. Here we identified overexpression of miR-16 and down-regulation of A2aAR in the colonic mucosa of active UC patients. We demonstrated that miR-16 negatively regulated the expression of the A2aAR at the post-transcriptional level. Furthermore, transfection of miR-16 mimics promoted nuclear translocation of NF-κB p65 protein and expression of pro-inflammatory cytokines, IFN-γ and IL-8 in colonic epithelial cells. Treatment with miR-16 inhibitor could reverse these effects in cells. The A2aAR-mediated effects of miR-16 on the activation of the NF-κB signaling pathway were confirmed by the A2aAR knockdown assay. Our results suggest that miR-16 regulated the immune and inflammatory responses, at least in part, by suppressing the expression of the A2aAR to control the activation of the NF-κB signaling pathway.
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
authors.forename: Shicai
authors.initials: S
authors.lastname: Ye
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
authors.forename: Weiyun
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
authors.forename: Wenkai
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
authors.forename: Caiyuan
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
authors.forename: Juxiang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
authors.forename: Zonghao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Pei
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
authors.forename: Hesheng
authors.initials: H
authors.lastname: Luo
mesh_terms: D020413:3' Untranslated Regions; D003093:Colitis, Ulcerative / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D016207:Cytokines; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A