title: MicroRNA-206 is involved in the pathogenesis of ulcerative colitis via regulation of adenosine A3 receptor.
abstract: Increasing evidence suggests that miRNAs are widely dysregulated in ulcerative colitis (UC), potentially affecting UC pathogenesis, diagnosis, and therapy. microRNA (miR) -206 has been reported to be upregulated in UC; however, its function and role in UC remain unknown. Here, we elucidate the function of miR-206 in the pathogenesis of UC. In patients with active-UC, miR-206 and adenosine A3 receptor (A3AR) levels were significantly upregulated and downregulated, respectively, and were inversely correlated. A3AR was expressed in the colon mucosa (particularly in colon epithelial-cell membranes). In HT-29 cells, miR-206 downregulated A3AR mRNA/protein expression by directly targeting the A3AR 3'-UTR; miR-206 overexpression and knockdown respectively increased and decreased TNF-α-induced nuclear NF-κB/p65, p-IκB-α, IKKα, p-IKKα and IL-8/IL-1β secretion. However, A3AR-siRNA reversed the miR-206 inhibitory effect. Furthermore, miR-206 increased dextran sodium sulphate-induced colitis severity (i.e., increased bodyweight loss, DAI score, colon shrinkage, and MPO activity), which was partially ameliorated by miR-206-antagomir treatment. miR-206-agomir treatment potently suppressed A3AR expression and increased NF-κB signalling and downstream cytokine (TNF-α/IL-8/IL-1β) expression in the mouse colon, in contrast to miR-206-antagomir administration. Taken together, our results demonstrated that miR-206 has a proinflammatory role in UC by downregulating A3AR expression and activating NF-κB signalling.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Weiyun
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Yanting
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Shicai
authors.initials: S
authors.lastname: Ye
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Wenkai
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Caiyuan
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Juxiang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D020868:Gene Silencing; D019073:HT29 Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D043684:Receptor, Adenosine A3 / Q000235:genetics* / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D016207:Cytokines; D018836:Inflammation Mediators; C546087:MIRN206 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D043684:Receptor, Adenosine A3
keywords: NF-κB; adenosine A3 receptor; miRNA-206; ulcerative colitis