https://doi.org/10.4081/ejh.2022.3316

Effects of miR-939 and miR-376A on ulcerative colitis using a decoy strategy to inhibit NF-κB and NFAT expression

Vol. 66 No. 1 (2022)
Submitted: 8 August 2021
Accepted: 9 December 2021
Published: 15 February 2022
miR-939, miR-376A, NF-κB, NFAT, decoy strategy, ulcerative colitis
Abstract Views: 1359
PDF: 514
HTML: 19
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Yongwei Lin
Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Zhipeng Zhou
Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Lang Xie
Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Yongsheng Huang
Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Zhenghua Qiu
Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Lili Ye
Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Chunhui Cui
drcuich@163.com
https://orcid.org/0000-0001-7338-519X
Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

The aim of this study was to explore the effects of miR-939 and miR-376A on the pathogenesis of ulcerative colitis (UC) by using a decoy strategy to regulate the expression of nuclear transcription factor kappa B (NF-κB) and nuclear factor of activated T cells (NFAT). Such strategies represent a potential novel treatment for UC. Quantitative polymerase chain reaction (qPCR) analysis was used to detect the differences between the expression of miR-939, miR-376a, NF-κB, NFAT in the tissue samples from the resting and active stages of UC and healthy controls, and analyzed the correlation. The electrophoretic mobility shift assay was used to validate the ability of miRNAs to bind to NF-κB and NFAT. The expression of components of the intestinal barrier in UC and changes in apoptosis-related factors were examined by western blotting, qPCR, and immunofluorescence. After a dextran sulfate sodium (DSS)-induced mouse model of UC was established, the morphological changes in the colonic tissues of mice, the changes in serum inflammatory factors, and the changes in urine protein or urine leukocytes, liver enzymes, and prothrombin time were measured to examine intestinal permeability. The expression of miR-939 and miR-376a in human UC tissue was significantly lower than that in the normal control tissue, and was negatively correlated with the expression of NF-κB and NFAT. miR-939 and miR-376a decoy strategies resulted in a beneficial increase in the expression of claudins, occludins, and ZO-1 protein and inhibited apoptosis in intestinal epithelial cells. The disease activity index of the UC model group was significantly higher than that of the normal control group. The expression of inflammatory factors in the decoy group was higher than that in the UC model group. Therefore, from the experimental results, it can be concluded that using miR-939 and miR-376a to trap NF-κB and NFAT inhibits the activation of transcription factors NF-κB and NFAT, which in turn inhibits the expression of inflammatory factors and results in partial recovery of the intestinal barrier in UC. The decoy strategy inhibited apoptosis in the target cells and had a therapeutic effect in the mice model of UC. This study provides new ideas for the development of future clinical therapies for UC.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Crossref
Scopus
Google Scholar
Europe PMC
Herrlinger K. Inflammatory bowel disease: an overview. Med Monatsschr Pharm 2013;36:402-8.
Eisenstein M. Ulcerative colitis: towards remission. Nature 2018;563:S33. DOI: https://doi.org/10.1038/d41586-018-07276-2
da Silva BC, Lyra AC, Rocha R, Santana GO. Epidemiology, demographic characteristics and prognostic predictors of ulcerative colitis. World J Gastroenterol 2014;20:9458-67. DOI: https://doi.org/10.3748/wjg.v20.i28.9458
Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 2017;390:2769-78. DOI: https://doi.org/10.1016/S0140-6736(17)32448-0
Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. Lancet 2017;389:1756-70. DOI: https://doi.org/10.1016/S0140-6736(16)32126-2
Yamamoto-Furusho JK, Gutiérrez-Grobe Y, López-Gómez JG, Bosques-Padilla F, Rocha-Ramírez JL, Grupo del Consenso Mexicano de Colitis Ulcerosa Crónica Idiopática. The Mexican consensus on the diagnosis and treatment of ulcerative colitis. Rev Gastroenterol Mex (Engl Ed) 2018;83:144-67. DOI: https://doi.org/10.1016/j.rgmx.2017.08.006
Lan F, Yue X, Ren G, Li H, Ping L, Wang Y, et al. miR-15a/16 enhances radiation sensitivity of non-small cell lung cancer cells by targeting the TLR1/NF-κB signaling pathway. Int J Radiat Oncol Biol Phys 2015;91:73-81. DOI: https://doi.org/10.1016/j.ijrobp.2014.09.021
Zhou J, Ping FF, Lv WT, Feng JY, Shang J. Interleukin-18 directly protects cortical neurons by activating PI3K/AKT/NF-κB/CREB pathways. Cytokine 2014;69:29-38. DOI: https://doi.org/10.1016/j.cyto.2014.05.003
Yang HJ, Wang M, Wang L, Cheng BF, Lin XY, Feng ZW. NF-κB regulates caspase-4 expression and sensitizes neuroblastoma cells to fas-induced apoptosis. PLoS One 2015;10:e0117953. DOI: https://doi.org/10.1371/journal.pone.0117953
Goto T, Fukui A, Shibuya H, Keller R, Asashima M. Xenopus furry contributes to release of microRNA gene silencing. Proc Natl Acad Sci USA 2010;107:19344-9. DOI: https://doi.org/10.1073/pnas.1008954107
McKenna LB, Schug J, Vourekas A, McKenna JB, Bramswig NC, Friedman JR, et al. MicroRNAs control intestinal epithelial differentiation, architecture, and barrier function. Gastroenterology 2010;139:1654-64. DOI: https://doi.org/10.1053/j.gastro.2010.07.040
Ahmad MZ, Akhter S, Mallik N, Anwar M, Tabassum W, Ahmad FJ. Application of decoy oligonucleotides as novel therapeutic strategy: a contemporary overview. Curr Drug Discov Technol 2013;10:71-84. DOI: https://doi.org/10.2174/1570163811310010009
Remes A, Wagner AH, Schmiedel N, Heckmann M, Ruf T, Ding L, et al. AAV-mediated expression of NFAT decoy oligonucleotides protects from cardiac hypertrophy and heart failure. Basic Res Cardiol 2021;116:38. DOI: https://doi.org/10.1007/s00395-021-00880-w
Kim KH, Park JH, Lee WR, Park JS, Kim HC, Park KK. The inhibitory effect of chimeric decoy oligodeoxynucleotide against NF-κB and Sp1 in renal interstitial fibrosis. J Mol Med (Berl) 2013;91:573-86. DOI: https://doi.org/10.1007/s00109-012-0972-2
Correia de Sousa M, Gjorgjieva M, Dolicka D, Sobolewski C, Foti M. Deciphering miRNAs' Action through miRNA Editing. Int J Mol Sci 2019;20:6249. DOI: https://doi.org/10.3390/ijms20246249
Chunhui C, Jinlong Y, Shuxin H, Huiquan Z, Zonghai H. transcriptional regulation of gene expression by microRNAs as endogenous decoys of transcription factors. Cell Physiol Biochemistry 2014;33:1698-14. DOI: https://doi.org/10.1159/000362952
Atreya I, Atreya R, Neurath MF. NF-kappaB in inflammatory bowel disease. J Intern Med 2008;263:591-6.
Chand S, Mehta N, Bahia MS, Dixit A, Silakari O. Protein kinase C-theta inhibitors: a novel therapy for inflammatory disorders. Curr Pharm Des 2012;18:4725-46. DOI: https://doi.org/10.2174/138161212802651625
Kornbluth A, Sachar DB, Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 2004;99:1371-85. Erratum in Am J Gastroenterol 2010;105:500. DOI: https://doi.org/10.1111/j.1572-0241.2004.40036.x
Wang YF, Ouyang Q, Hu RW. Progression of inflammatory bowel disease in China. J Dig Dis 2010;11:76-82. DOI: https://doi.org/10.1111/j.1751-2980.2010.00421.x
Li L, Miao X, Ni R, Miao X, Wang L, Gu X, et al. Epithelial-specific ETS-1 (ESE1/ELF3) regulates apoptosis of intestinal epithelial cells in ulcerative colitis via accelerating NF-κB activation. Immunol Res 2015;62:198-212. DOI: https://doi.org/10.1007/s12026-015-8651-3
Matricon J, Barnich N, Ardid D. Immunopathogenesis of inflammatory bowel disease. Self Nonself 2010;1:299-309. DOI: https://doi.org/10.4161/self.1.4.13560
Mennigen R, Nolte K, Rijcken E. Probiotic mixture VSL3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Am J Physiol Gastrointest Liver Physiol 2009;296:G1140-9. DOI: https://doi.org/10.1152/ajpgi.90534.2008
Oshima T, Miwa H, Joh T. Changes in the expression of claudins in active ulcerative colitis. J Gastroenterol Hepatol 2008;23:S146-50. DOI: https://doi.org/10.1111/j.1440-1746.2008.05405.x
Jacknowitz AI. Ulcerative colitis and its treatment. Am J Hosp Pharm 1980;37:1635-46. DOI: https://doi.org/10.1093/ajhp/37.12.1635
Tang P, Xiong Q, Ge W, Zhang L. The role of microRNAs in osteoclasts and osteoporosis. RNA Biol 2014;11:1355-63. DOI: https://doi.org/10.1080/15476286.2014.996462
Rencz F, Péntek M, Bortlik M, Zagorowicz E, Hlavaty T, Śliwczyński A, et al. Biological therapy in inflammatory bowel diseases: Access in Central and Eastern Europe. World J Gastroenterol 2015;21:1728-37. DOI: https://doi.org/10.3748/wjg.v21.i6.1728
Atreya I, Atreya R, Neurath MF. NF-kappaB in inflammatory bowel disease. J Intern Med 2008;263:591-6. DOI: https://doi.org/10.1111/j.1365-2796.2008.01953.x
Vora P, McGovern DP. LRRK2 as a negative regulator of NFAT: implications for the pathogenesis of inflammatory bowel disease. Expert Rev Clin Immunol 2012;8:227-9. DOI: https://doi.org/10.1586/eci.12.11

How to Cite

Lin, Y., Zhou, Z., Xie, L., Huang, Y., Qiu, Z., Ye, L., & Cui, C. (2022). Effects of miR-939 and miR-376A on ulcerative colitis using a decoy strategy to inhibit NF-κB and NFAT expression. European Journal of Histochemistry, 66(1). https://doi.org/10.4081/ejh.2022.3316
Copyright (c) 2022 The Author(s) Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.


Similar Articles

<< < 1 2 3 4 5 6 7 8 9 10 > >> 

You may also start an advanced similarity search for this article.