MicroRNA‑7‑5p regulates the expression of TFF3 in inflammatory bowel disease

Guo,Jing; Sun,Mei; Teng,Xu; Xu,Lingfen

doi:10.3892/mmr.2017.6730

MicroRNA‑7‑5p regulates the expression of TFF3 in inflammatory bowel disease

Authors:
- Jing Guo
- Mei Sun
- Xu Teng
- Lingfen Xu
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Affiliations: Department of Pediatrics, The Affiliated Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: June 8, 2017 https://doi.org/10.3892/mmr.2017.6730
Pages: 1200-1206
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Trefoil factor 3 (TFF3) serves an important role in intestinal mucosal damage and healing, and contributes to the pathogenesis and treatment of inflammatory bowel disease (IBD). The aim of the present study was to determine the association between TFF3 and microRNA‑7‑5p (miR‑7‑5p) in IBD. Tissue immunohistochemistry was applied to evaluate the relative expression of TFF3, and reverse transcription‑quantitative polymerase chain reaction was performed to determine the expression of miR‑7‑5p in lesional tissue obtained from patients with IBD and healthy control tissues. A dual‑luciferase reporter assay was used to investigate whether TFF3 was a target of miR‑7‑5p, and western blotting was performed to determine the expression of TFF3 when miR‑7‑5p was overexpressed or suppressed. The protein expression levels of TFF3 were decreased and miR‑7‑5p was overexpressed in the lesional tissue of patients with IBD compared with in healthy control tissues. TFF3 was identified as a target of miR‑7‑5p, and TFF3 protein expression was negatively regulated by miR‑7‑5p in human colonic epithelial LS174T cells. The present study demonstrated a negative association between the expression of miR‑7‑5p and TFF3 in IBD lesional tissues and normal tissues. In conclusion, TFF3 was identified as a novel target of miR‑7‑5p and miR‑7‑5p may serve as a promising therapeutic target for IBD.

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1	Madsen JR, Laursen LS and Lauritsen K: Chronic inflammatory bowel disease-current status. Ugeskr Laeger. 154:2243–2250. 1992.(In Danish). PubMed/NCBI
2	Ng SC, Zeng Z, Niewiadomski O, Tang W, Bell S, Kamm MA, Hu P, de Silva HJ, Niriella MA, Udara WS, et al: Early course of inflammatory bowel disease in a population-based inception cohort study from 8 countries in Asia and Australia. Gastroenterology. 150:82–95. e3; quiz e13-e14. 2016. View Article : Google Scholar : PubMed/NCBI
3	Kjellev S: The trefoil factor family-small peptides with multiple functionalities. Cell Mol Life Sci. 66:1350–1369. 2009. View Article : Google Scholar : PubMed/NCBI
4	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
5	Stanczyk J, Pedrioli DM, Brentano F, Sanchez-Pernaute O, Kolling C, Gay RE, Detmar M, Gay S and Kyburz D: Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum. 58:1001–1009. 2008. View Article : Google Scholar : PubMed/NCBI
6	Tang Y, Luo X, Cui H, Ni X, Yuan M, Guo Y, Huang X, Zhou H, de Vries N, Tak PP, et al: MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum. 60:1065–1075. 2009. View Article : Google Scholar : PubMed/NCBI
7	Tan Z, Randall G, Fan J, Camoretti-Mercado B, Brockman-Schneider R, Pan L, Solway J, Gern JE, Lemanske RF, Nicolae D and Ober C: Allele-specific targeting of microRNAs to HLA-G and risk of asthma. Am J Hum Genet. 81:829–834. 2007. View Article : Google Scholar : PubMed/NCBI
8	Fasseu M, Tréton X, Guichard C, Pedruzzi E, Cazals-Hatem D, Richard C, Aparicio T, Daniel F, Soulé JC, Moreau R, et al: Identification of restricted subsets of mature microRNA abnormally expressed in inactive colonic mucosa of patients with inflammatory bowel disease. PLoS One. 5:pii: e131602010. View Article : Google Scholar
9	Sheedy FJ, Palsson-McDermott E, Hennessy EJ, Martin C, O'Leary JJ, Ruan Q, Johnson DS, Chen Y and O'Neill LA: Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol. 11:141–147. 2010. View Article : Google Scholar : PubMed/NCBI
10	McKenna LB, Schug J, Vourekas A, McKenna JB, Bramswig NC, Friedman JR and Kaestner KH: MicroRNAs control intestinal epithelial differentiation, architecture, and barrier function. Gastroenterology. 139:1654–1664, e1. 2010. View Article : Google Scholar : PubMed/NCBI
11	Ye D, Guo S, Al-Sadi R and Ma TY: MicroRNA regulation of intestinal epithelial tight junction permeability. Gastroenterology. 141:1323–1333. 2011. View Article : Google Scholar : PubMed/NCBI
12	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
13	Bansal A, Lee IH, Hong X, Anand V, Mathur SC, Gaddam S, Rastogi A, Wani SB, Gupta N, Visvanathan M, et al: Feasibility of microRNAs as biomarkers for Barrett's Esophagus progression: A pilot cross-sectional, phase 2 biomarker study. Am J Gastroenterol. 106:1055–1063. 2011. View Article : Google Scholar : PubMed/NCBI
14	Olaru AV, Selaru FM, Mori Y, Vazquez C, David S, Paun B, Cheng Y, Jin Z, Yang J, Agarwal R, et al: Dynamic changes in the expression of MicroRNA-31 during inflammatory bowel disease-associated neoplastic transformation. Inflamm Bowel Dis. 17:221–231. 2011. View Article : Google Scholar : PubMed/NCBI
15	Kanaan Z, Rai SN, Eichenberger MR, Barnes C, Dworkin AM, Weller C, Cohen E, Roberts H, Keskey B, Petras RE, et al: Differential microRNA expression tracks neoplastic progression in inflammatory bowel disease-associated colorectal cancer. Hum Mutat. 33:551–560. 2012. View Article : Google Scholar : PubMed/NCBI
16	Wu F, Guo NJ, Tian H, Marohn M, Gearhart S, Bayless TM, Brant SR and Kwon JH: Peripheral blood microRNAs distinguish active ulcerative colitis and Crohn's disease. Inflamm Bowel Dis. 1:241–250. 2011. View Article : Google Scholar
17	Henderson P and Wilson DC: The rising incidence of paediatric-onset inflammatory bowel disease. Arch Dis Child. 97:585–586. 2012. View Article : Google Scholar : PubMed/NCBI
18	Wang XQ, Zhang Y, Xu CD, Jiang LR, Huang Y, Du HM and Wang XJ: Inflammatory bowel disease in Chinese children: A multicenter analysis over a decade from Shanghai. Inflamm bowel Dis. 19:423–428. 2013. View Article : Google Scholar : PubMed/NCBI
19	Sun Z, Liu H, Yang Z, Shao D, Zhang W, Ren Y, Sun B, Lin J, Xu M and Nie S: Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage. Int J Oncol. 45:1123–1132. 2014.PubMed/NCBI
20	Kindon H, Pothoulakis C, Thim L, Lynch-Devaney K and Podolsky DK: Trefoil peptide protection of intestinal epithelial barrier function: Cooperative interaction with mucin glycoprotein. Gastroenterology. 109:516–523. 1995. View Article : Google Scholar : PubMed/NCBI
21	Marchbank T, Cox HM, Goodlad RA, Giraud AS, Moss SF, Poulsom R, Wright NA, Jankowski J and Playford RJ: Effect of ectopic expression of rat trefoil factor family 3 (intestinal trefoil factor) in the jejunum of transgenic mice. J Biol Chem. 276:24088–24096. 2001. View Article : Google Scholar : PubMed/NCBI
22	Mashimo H, Wu DC, Podolsky DK and Fishman MC: Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor. Science. 274:262–265. 1996. View Article : Google Scholar : PubMed/NCBI
23	Xu LF, Teng X, Guo J and Sun M: Protective effect of intestinal trefoil factor on injury of intestinal epithelial tight junction induced by platelet activating factor. Inflammation. 35:308–315. 2012. View Article : Google Scholar : PubMed/NCBI
24	Xu LF, Xu C, Mao ZQ, Teng X, Ma L and Sun M: Disruption of the F-actin cytoskeleton and monolayer barrier integrity induced by PAF and the protective effect of ITF on intestinal epithelium. Arch Pharm Res. 34:245–251. 2011. View Article : Google Scholar : PubMed/NCBI
25	Ma J, Fang B, Zeng F, Pang H, Zhang J, Shi Y, Wu X, Cheng L, Ma C, Xia J and Wang Z: Curcumin inhibits cell growth and invasion through up-regulation of miR-7 in pancreatic cancer cells. Toxicol Lett. 231:82–91. 2014. View Article : Google Scholar : PubMed/NCBI
26	Fang Y, Xue JL, Shen Q, Chen J and Tian L: MicroRNA-7 inhibits tumor growth and metastasis by targeting the phosphoinositide 3-kinase/Akt pathway in hepatocellular carcinoma. Hepatology. 55:1852–1862. 2012. View Article : Google Scholar : PubMed/NCBI
27	Xu K, Chen Z, Qin C and Song X: miR-7 inhibits colorectal cancer cell proliferation and induces apoptosis by targeting XRCC2. Onco Targets Ther. 7:325–332. 2014. View Article : Google Scholar : PubMed/NCBI
28	Nguyen HT, Dalmasso G, Yan Y, Laroui H, Dahan S, Mayer L, Sitaraman SV and Merlin D: MicroRNA-7 modulates CD98 expression during intestinal epithelial cell differentiation. J Biol Chem. 285:1479–1489. 2010. View Article : Google Scholar : PubMed/NCBI
29	Pekow JR and Kwon JH: MicroRNAs in inflammatory bowel disease. Inflamm Bowel Dis. 18:187–193. 2012. View Article : Google Scholar : PubMed/NCBI