Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
February-2020 Volume 19 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
February-2020 Volume 19 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

The role of the miR‑21‑5p‑mediated inflammatory pathway in ulcerative colitis

  • Authors:
    • Xiaohong Lu
    • Yuanjie Yu
    • Shiyun Tan
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Digestive System Disease, Wuhan, Hubei 430060, P.R. China
    Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 981-989
    |
    Published online on: December 4, 2019
       https://doi.org/10.3892/etm.2019.8277
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Ulcerative colitis (UC), a major type of inflammatory bowel disease, is also a chronic non‑specific intestinal inflammation condition of unknown etiology. The pathogenesis of UC is closely associated with immune abnormalities, inflammatory damage and genetics. The present study aimed to explore the effects of microRNA (miR)‑21‑5p on the interleukin‑6 (IL‑6) receptor (IL6R)/signal transducer and activator of transcription (STAT3) signal pathway in UC, in order to identify a highly effective treatment for UC. A total of 45 patients with UC and 45 healthy controls were recruited for the present study. The expression levels of miR‑21‑5p and STAT3 in the sera of patients with UC and healthy controls were determined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). A UC rat model was established using dextran sulfate sodium. Following lipopolysaccharide (LPS) treatment, RAW264.7 cells were transfected with a miR‑21‑5p inhibitor. The levels of morphological damage and apoptosis of the colonic mucosal epithelial tissue were investigated using hematoxylin and eosin staining and a TUNEL staining assay, and then the colon macroscopic damage index and disease activity index were measured in rats. Western blot analysis was used to detect the protein expression levels of IL6R, STAT3, intracellular adhesion molecule 1 (ICAM‑1), NF‑κB, cleaved caspase‑3, cleaved caspase‑9 and Fas ligand (FasL). RT‑qPCR detected the mRNA expression levels of miR‑21‑5p, IL6R, STAT3, ICAM‑1, NF‑κB, caspase‑3, caspase‑9 and FasL. An ELISA was performed to measure the levels of inflammatory cytokines. The viability and apoptosis levels of RAW264.7 cells were examined using MTT and flow cytometry assays. Additionally, STAT3 was investigated as a direct target of miR‑21‑5p in RAW264.7 cells using a dual‑luciferase reporter assay. The results of the present study demonstrated that inflammation and apoptotic markers were revealed to be significantly downregulated following transfection with miR‑21‑5p inhibitors in RAW264.7 cells induced by LPS, and that cell viability was increased. Furthermore, STAT3 was confirmed to be a target of miR‑21‑5p in RAW264.7 cells. Collectively, these data demonstrated that miR‑21‑5p inhibition mediated the IL‑6/STAT3 pathway in UC rats to decrease the levels of inflammation and apoptosis in RAW264.7 cells, and suggested that miR‑21‑5p may be an important therapy target in human UC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Ordás I, Eckmann L, Talamini M, Baumgart DC and Sandborn WJ: Ulcerative colitis. Lancet. 380:1606–1619. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Gillen CD, Walmsley RS, Prior P, Andrews HA and Allan RN: Ulcerative colitis and Crohn's disease: A comparison of the colorectal cancer risk in extensive colitis. Gut. 35:1590–1592. 1994. View Article : Google Scholar : PubMed/NCBI

3 

Wang Z: MicroRNA: A matter of life or death. World J Biol Chem. 1:41–54. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Kinose Y, Sawada K, Nakamura K and Kimura T: The role of MicroRNAs in ovarian cancer. Biomed Res Int. 2014:2493932014. View Article : Google Scholar : PubMed/NCBI

5 

Shen N, Huang X and Li J: Upregulation of miR-129-5p affects laryngeal cancer cell proliferation, invasiveness, and migration by affecting STAT3 expression. Tumour Biol. 37:1789–1796. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Yang Y, Ma Y, Shi C, Chen H, Zhang H, Chen N, Zhang P, Wang F, Yang J, Yang J, et al: Overexpression of miR-21 in patients with ulcerative colitis impairs intestinal epithelial barrier function through targeting the Rho GTPase RhoB. Biochem Biophys Res Commun. 434:746–752. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Polytarchou C, Hommes DW, Palumbo T, Hatziapostolou M, Koutsioumpa M, Koukos G, van der Meulen-de Jong AE, Oikonomopoulos A, van Deen WK, Vorvis C, et al: MicroRNA214 is associated with progression of ulcerative colitis, and inhibition reduces development of colitis and colitis-associated cancer in mice. Gastroenterology. 149:981–992.e11. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Ranjha R, Meena NK, Singh A, Ahuja V and Paul J: Association of miR-196a-2 and miR-499 variants with ulcerative colitis and their correlation with expression of respective miRNAs. PLoS One. 12:e01734472017. View Article : Google Scholar : PubMed/NCBI

9 

Lewis A, Felice C, Kumagai T, Lai C, Singh K, Jeffery RR, Feakins R, Giannoulatou E, Armuzzi A, Jawad N, et al: The miR-200 family is increased in dysplastic lesions in ulcerative colitis patients. PLoS One. 12:e01736642017. View Article : Google Scholar : PubMed/NCBI

10 

Shi CC: Study on the mechanism of miRNA-21 in regulating intestinal barrier function and inflammation related colon cancer. Shanghai Jiaotong University; 2014

11 

Thorlacius-Ussing G, Nielsen BS, Andersen V, Holmstrøm K and Pedersen AE: Expression and localization of miR-21 and miR-126 in mucosal tissue from patients with inflammatory bowel disease. Inflamm Bowel Dis. 23:739–752. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Gryshkova V, Fleming A, McGhan P, De Ron P, Fleurance R, Valentin JP and Nogueira da Costa A: miR-21-5p as a potential biomarker of inflammatory infiltration in the heart upon acute drug-induced cardiac injury in rats. Toxicol Lett. 286:31–38. 2018. View Article : Google Scholar : PubMed/NCBI

13 

Buoli Comani G, Panceri R, Dinelli M, Biondi A, Mancuso C, Meneveri R and Barisani D: miRNA-regulated gene expression differs in celiac disease patients according to the age of presentation. Genes Nutr. 10:4822015. View Article : Google Scholar : PubMed/NCBI

14 

Zhang T: Study on the relationship between intestinal barrier and STAT3 signaling pathway in ulcerative colitis. Tianjin Medical University; 2013

15 

Li T, Zhu XD, Yang Y and Zhai YH: Effect of tongxie yaofang on the expression of IL-6 and IL6R in the hypothalamus of rats with ulcerative colitis. Chin J Exp Trad Med Formulae. 23:103–108. 2017.

16 

Wang Q, Bie YL, Wang D and Fan WT: Effect of dandelion polysaccharide on IL-6 /STAT3 signaling pathway in ulcerative colitis rats. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 33:422–425. 2017.(In Chinese). PubMed/NCBI

17 

Murthy S, Cooper HS, Yoshitake H, Meyer C, Meyer CJ and Murthy NS: Combination therapy of pentoxifylline and TNFalpha monoclonal antibody in dextran sulphate-induced mouse colitis. Aliment Pharmacol Ther. 13:251–260. 1999. View Article : Google Scholar : PubMed/NCBI

18 

Cooper HS, Murthy SN, Shah RS and Sedergran DJ: Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 69:238–249. 1993.PubMed/NCBI

19 

Paiotti AP, Ribeiro DA, Silva RM, Marchi P, Oshima CT, Neto RA, Miszputen SJ and Franco M: Effect of COX-2 inhibitor lumiracoxib, the anti-TNF-α etanercept and your association on TNBS-induced colitis in Wistar rats. J Mol Histol. 43:307–317. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Dieleman LA, Palmen MJ, Akol H, Bloemena E, Peña AS, Meuwissen SG and Van Rees EP: Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol. 114:385–391. 1998. View Article : Google Scholar : PubMed/NCBI

21 

Agarwal V, Bell GW, Nam J and Bartel DP: Predicting effective microRNA target sites in mammalian mRNAs. Elife. 4:e050052015. View Article : Google Scholar

22 

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

23 

Li Z, Wang Y and Zhu Y: Association of miRNA-146a rs2910164 and miRNA-196 rs11614913 polymorphisms in patients with ulcerative colitis: A meta-analysis and review. Medicine (Baltimore). 97:e122942018. View Article : Google Scholar : PubMed/NCBI

24 

Deng S, Wang H, Fan H, Zhang L, Hu J, Tang Q, Shou Z, Liu X, Zuo D, Yang J, et al: Over-expressed miRNA-200b ameliorates ulcerative colitis-related colorectal cancer in mice through orchestrating epithelial-mesenchymal transition and inflammatory responses by channel of AKT2. Int Immunopharmacol. 61:346–354. 2018. View Article : Google Scholar : PubMed/NCBI

25 

Huang Y, Ma Z, Cui YH, Dong HS, Zhao JM, Dou CZ, Liu HR, Li J and Wu HG: Effects of herb-partitioned moxibustion on the miRNA expression profiles in colon from rats with DSS-induced ulcerative colitis. Evid Based Complement Alternat Med. 2017:7673012017. View Article : Google Scholar

26 

Liu Z, Yu M, Fei B, Fang X, Ma T and Wang D: miR-21-5p targets PDHA1 to regulate glycolysis and cancer progression in gastric cancer. Oncol Rep. 40:2955–2963. 2018.PubMed/NCBI

27 

Fromm B, Tosar JP, Lu Y, Halushka MK and Witwer KW: Human and cow have identical miR-21-5p and miR-30a-5p sequences, which are likely unsuited to study dietary uptake from cow milk. J Nutr. 148:1506–1507. 2018. View Article : Google Scholar : PubMed/NCBI

28 

Li Q, Li B, Li Q, Wei S, He Z, Huang X, Wang L, Xia Y, Xu Z, Li Z, et al: Exosomal miR-21-5p derived from gastric cancer promotes peritoneal metastasis via mesothelial-to-mesenchymal transition. Cell Death Dis. 9:8542018. View Article : Google Scholar : PubMed/NCBI

29 

Li XH, Chen D, Li M, Gao X, Shi G and Zhao H: The CADM2/Akt pathway is involved in the inhibitory effect of miR-21-5p downregulation on proliferation and apoptosis in esophageal squamous cell carcinoma cells. Chem Biol Interact. 288:76–82. 2018. View Article : Google Scholar : PubMed/NCBI

30 

Lakhter AJ, Pratt RE, Moore RE, Doucette KK, Maier BF, DiMeglio LA and Sims EK: Beta cell extracellular vesicle miR-21-5p cargo is increased in response to inflammatory cytokines and serves as a biomarker of type 1 diabetes. Diabetologia. 61:1124–1134. 2018. View Article : Google Scholar : PubMed/NCBI

31 

Ge XT, Huang S, Gao H, Han Z, Chen F, Zhang S, Wang Z, Kang C, Jiang R, Yue S, et al: miR-21-5p alleviates leakage of injured brain microvascular endothelial barrier in vitro through suppressing inflammation and apoptosis. Brain Res. 1650:31–40. 2016. View Article : Google Scholar : PubMed/NCBI

32 

Hua Y, Drew P and Richard J: STATs in cancer inflammation and immunity: A leading role for STAT3. Nat Rev Cancer. 9:798–809. 2009. View Article : Google Scholar : PubMed/NCBI

33 

Dang V, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, Bordman Z, Fu J, Kim Y, Yen HR, et al: Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell. 146:772–784. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Liu JZ, Suzanne VS, Hailiang H, Ng SC, Alberts R, Takahashi A, Ripke S, Lee JC, Jostins L, Shah T, et al: Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet. 47:979–986. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Lu X, Yu Y and Tan S: The role of the miR‑21‑5p‑mediated inflammatory pathway in ulcerative colitis. Exp Ther Med 19: 981-989, 2020.
APA
Lu, X., Yu, Y., & Tan, S. (2020). The role of the miR‑21‑5p‑mediated inflammatory pathway in ulcerative colitis. Experimental and Therapeutic Medicine, 19, 981-989. https://doi.org/10.3892/etm.2019.8277
MLA
Lu, X., Yu, Y., Tan, S."The role of the miR‑21‑5p‑mediated inflammatory pathway in ulcerative colitis". Experimental and Therapeutic Medicine 19.2 (2020): 981-989.
Chicago
Lu, X., Yu, Y., Tan, S."The role of the miR‑21‑5p‑mediated inflammatory pathway in ulcerative colitis". Experimental and Therapeutic Medicine 19, no. 2 (2020): 981-989. https://doi.org/10.3892/etm.2019.8277
Copy and paste a formatted citation
x
Spandidos Publications style
Lu X, Yu Y and Tan S: The role of the miR‑21‑5p‑mediated inflammatory pathway in ulcerative colitis. Exp Ther Med 19: 981-989, 2020.
APA
Lu, X., Yu, Y., & Tan, S. (2020). The role of the miR‑21‑5p‑mediated inflammatory pathway in ulcerative colitis. Experimental and Therapeutic Medicine, 19, 981-989. https://doi.org/10.3892/etm.2019.8277
MLA
Lu, X., Yu, Y., Tan, S."The role of the miR‑21‑5p‑mediated inflammatory pathway in ulcerative colitis". Experimental and Therapeutic Medicine 19.2 (2020): 981-989.
Chicago
Lu, X., Yu, Y., Tan, S."The role of the miR‑21‑5p‑mediated inflammatory pathway in ulcerative colitis". Experimental and Therapeutic Medicine 19, no. 2 (2020): 981-989. https://doi.org/10.3892/etm.2019.8277
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team