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
July-2021 Volume 22 Issue 1

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
July-2021 Volume 22 Issue 1

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

miR‑489‑3p inhibits TLR4/NF‑κB signaling to prevent inflammation in psoriasis

  • Authors:
    • Yujian Ye
    • Ping Wang
    • Fangmei Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Dermatology, The Third People's Hospital of Hangzhou, Hangzhou, Zhejiang 310009, P.R. China, College of Medical Technology, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
    Copyright: © Ye et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 744
    |
    Published online on: May 11, 2021
       https://doi.org/10.3892/etm.2021.10176
  • 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

Psoriasis is a chronic inflammatory skin disease whose etiology has not yet been determined. MicroRNAs (miRs) regulate the early stages of psoriasis and are targets for therapeutic intervention. The present study aimed to investigate the functional role of miR‑489‑3p in psoriasis. The present study first assessed the expression levels of miR‑489‑3p and Toll‑like receptor (TLR)4 mRNA using reverse transcription‑quantitative PCR, and also detected the protein expression levels of TLR4 and NF‑κB via western blot analysis. TargetScan and miRDB target gene prediction tools were used to confirm the regulation of Toll‑like receptor (TLR)4 by miR‑489‑3p. Moreover, a Cell Counting Kit (CCK)‑8 assay was conducted to evaluate cell viability, while cell cycle and colony formation assays were performed to evaluate cell proliferation. Human keratinocytes (HaCaT) were co‑transfected with TLR4‑small interfering RNA and miR‑489‑3p‑inhibitor plasmids, and analysis of cell proliferation and inflammatory cytokine secretion was performed using CCK‑8 assay and ELISA. It was found that miR‑489‑3p expression was downregulated in patients with psoriasis. Bioinformatics analysis identified that TLR4 was a direct target of miR‑489‑3p. This was confirmed via luciferase reporter assays in HaCaT cells. The overexpression of miR‑489‑3p inhibited the TLR4/NF‑κB signaling pathway and reduced cell proliferation. TLR4 silencing alleviated the effects of miR‑489‑3p, and enhanced cell proliferation and inflammatory cytokine secretion. Taken together, these data suggested that miR‑489‑3p may be a key effector of psoriasis, which promotes inflammatory responses by direct targeting of TLR4. miR‑489‑3p therefore represents a promising prognostic biomarker and therapeutic target for psoriasis treatment.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Langley RG, Krueger GG and Griffiths CE: Psoriasis: Epidemiology, clinical features, and quality of life. Ann Rheum Dis. 64 (Suppl 2):ii18–ii25. 2005.PubMed/NCBI View Article : Google Scholar

2 

Zhang K and Shen ZA: Research advances on immunological properties and gene regulation of skin keratinocytes. Zhonghua Shao Shang Za Zhi. 37:89–92. 2021.PubMed/NCBI View Article : Google Scholar : (In Chinese).

3 

Lowes MA, Bowcock AM and Krueger JG: Pathogenesis and therapy of psoriasis. Nature. 445:866–873. 2007.PubMed/NCBI View Article : Google Scholar

4 

Qureshi AA, Choi HK, Setty AR and Curhan GC: Psoriasis and the risk of diabetes and hypertension: A prospective study of US female nurses. Arch Dermatol. 145:379–382. 2009.PubMed/NCBI View Article : Google Scholar

5 

Guttman-Yassky E, Nograles KE and Krueger JG: Contrasting pathogenesis of atopic dermatitis and psoriasis-part I: Clinical and pathologic concepts. J Allergy Clin Immunol. 127:1110–1118. 2011.PubMed/NCBI View Article : Google Scholar

6 

Rizwan M and Khan A: Association of psoriasis and serum uric acid levels: A case control study. Pakistan Armed Forces Med J. 69:408–412. 2019.

7 

Pradyuth S, Rapalli VK, Gorantla S, Waghule T, Dubey SK and Singhvi G: Insightful exploring of microRNAs in psoriasis and its targeted topical delivery. Dermatol Ther. 33(e14221)2020.PubMed/NCBI View Article : Google Scholar

8 

Valencia-Sanchez MA, Liu J, Hannon GJ and Parker R: Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev. 20:515–524. 2006.PubMed/NCBI View Article : Google Scholar

9 

Rebane A and Akdis CA: MicroRNAs: Essential players in the regulation of inflammation. J Allergy Clin Immunol. 132:15–26. 2013.PubMed/NCBI View Article : Google Scholar

10 

Chang L, Liang J, Xia X and Chen X: miRNA-126 enhances viability, colony formation, and migration of keratinocytes HaCaT cells by regulating PI3 K/AKT signaling pathway. Cell Biol Int. 43:182–191. 2019.PubMed/NCBI View Article : Google Scholar

11 

Covert MW, Leung TH, Gaston JE and Baltimore D: Achieving stability of lipopolysaccharide-induced NF-kappaB activation. Science. 309:1854–1857. 2005.PubMed/NCBI View Article : Google Scholar

12 

Kyriakis JM and Avruch J: Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 81:807–869. 2001.PubMed/NCBI View Article : Google Scholar

13 

Wei W, Dejie L, Xiaojing S, Tiancheng W, Yongguo C, Zhengtao Y and Naisheng Z: Magnolol inhibits the inflammatory response in mouse mammary epithelial cells and a mouse mastitis model. Inflammation. 38:16–26. 2015.PubMed/NCBI View Article : Google Scholar

14 

Lowes MA, Suárez-Fariñas M and Krueger JG: Immunology of psoriasis. Annu Rev Immunol. 32:227–255. 2014.PubMed/NCBI View Article : Google Scholar

15 

Zhang C, Xiao C, Dang E, Cao J, Zhu Z, Fu M, Yao X, Liu Y, Jin B, Wang G and Li W: CD100-Plexin-B2 promotes the inflammation in psoriasis by activating NF-κB and the inflammasome in keratinocytes. J Invest Dermatol. 138:375–383. 2018.PubMed/NCBI View Article : Google Scholar

16 

Wu AG, Conway J, Barazani L, Roy B, Cline A and Pereira F: Is clear always clear? Comparison of psoriasis area and severity index (PASI) and the Physician's global assessment (PGA) in psoriasis clearance. Dermatol Ther (Heidelb). 10:1155–1163. 2020.PubMed/NCBI View Article : Google Scholar

17 

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.PubMed/NCBI View Article : Google Scholar

18 

Cai Y, Fleming C and Yan J: New insights of T cells in the pathogenesis of psoriasis. Cell Mol Immunol. 9:302–309. 2012.PubMed/NCBI View Article : Google Scholar

19 

Griffiths CE and Barker JN: Pathogenesis and clinical features of psoriasis. Lancet. 370:263–271. 2007.PubMed/NCBI View Article : Google Scholar

20 

Han G, Williams CA, Salter K, Garl PJ, Li AG and Wang XJ: A role for TGFbeta signaling in the pathogenesis of psoriasis. J Invest Dermatol. 130:371–377. 2010.PubMed/NCBI View Article : Google Scholar

21 

Tattersall D, Scott CA, Gray C, Zicha D and Kelsell DP: EKV mutant connexin 31 associated cell death is mediated by ER stress. Hum Mol Genet. 18:4734–4745. 2009.PubMed/NCBI View Article : Google Scholar

22 

Kalali BN, Köllisch G, Mages J, Müller T, Bauer S, Wagner H, Ring J, Lang R, Mempel M and Ollert M: Double-stranded RNA induces an antiviral defense status in epidermal keratinocytes through TLR3-, PKR-, and MDA5/RIG-I-mediated differential signaling. J Immunol. 181:2694–2704. 2008.PubMed/NCBI View Article : Google Scholar

23 

Aldehlawi H, Usman S, Lalli A, Ahmad F, Williams G, Teh MT and Waseem A: Serum lipids, retinoic acid and phenol red differentially regulate expression of keratins K1, K10 and K2 in cultured keratinocytes. Sci Rep. 10(4829)2020.PubMed/NCBI View Article : Google Scholar

24 

Ni X and Lai Y: Keratinocyte: A trigger or an executor of psoriasis? J Leukoc Biol. 108:485–491. 2020.PubMed/NCBI View Article : Google Scholar

25 

Tsuru Y, Jinnin M, Ichihara A, Fujisawa A, Moriya C, Sakai K, Fukushima S and Ihn H: miR-424 levels in hair shaft are increased in psoriatic patients. J Dermatol. 41:382–385. 2014.PubMed/NCBI View Article : Google Scholar

26 

Xu N, Brodin P, Wei T, Meisgen F, Eidsmo L, Nagy N, Kemeny L, Ståhle M, Sonkoly E and Pivarcsi A: MiR-125b, a microRNA downregulated in psoriasis, modulates keratinocyte proliferation by targeting FGFR2. J Invest Dermatol. 131:1521–1529. 2011.PubMed/NCBI View Article : Google Scholar

27 

Li J, Qu W, Jiang Y, Sun Y, Cheng Y, Zou T and Du S: miR-489 suppresses proliferation and invasion of human bladder cancer cells. Oncol Res. 24:391–398. 2016.PubMed/NCBI View Article : Google Scholar

28 

Liu Q, Yang G and Qian Y: Loss of MicroRNA-489-3p promotes osteosarcoma metastasis by activating PAX3-MET pathway. Mol Carcinog. 56:1312–1321. 2017.PubMed/NCBI View Article : Google Scholar

29 

Jiang R, Zhang C, Gu R and Wu H: MicroRNA-489-3p inhibits neurite growth by regulating PI3K/AKT pathway in spinal cord injury. Pharmazie. 72:272–278. 2017.PubMed/NCBI View Article : Google Scholar

30 

Banerjee S, Thompson WE and Chowdhury I: Emerging roles of microRNAs in the regulation of Toll-like receptor (TLR)-signaling. Front Biosci (Landmark Ed). 26:771–796. 2021.PubMed/NCBI

31 

Yamamoto M, Sato S, Hemmi H, Uematsu S, Hoshino K, Kaisho T, Takeuchi O, Takeda K and Akira S: TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat Immunol. 4:1144–1150. 2003.PubMed/NCBI View Article : Google Scholar

32 

Faure E, Equils O, Sieling PA, Thomas L, Zhang FX, Kirschning CJ, Polentarutti N, Muzio M and Arditi M: Bacterial lipopolysaccharide activates NF-kappaB through Toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells. Differential expression of TLR-4 and TLR-2 in endothelial cells. J Biol Chem. 275:11058–11063. 2000.PubMed/NCBI View Article : Google Scholar

33 

Muzio M, Natoli G, Saccani S, Levrero M and Mantovani A: The human Toll signaling pathway: Divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6). J Exp Med. 187:2097–2101. 1998.PubMed/NCBI View Article : Google Scholar

34 

Hayden MS and Ghosh S: . NF-κB, the first quarter-century: Remarkable progress and outstanding questions. Genes Dev. 26:203–234. 2012.PubMed/NCBI View Article : Google Scholar

35 

Vallabhapurapu S and Karin M: Regulation and function of NF-kappaB transcription factors in the immune system. Ann Rev Immunol. 27:693–733. 2009.PubMed/NCBI View Article : Google Scholar

36 

Sun W, Gao Y, Yu X, Yuan Y, Yi J, Zhang Z, Cheng Y, Li Y, Peng X and Cha X: ‘Psoriasis 1’ reduces psoriasis-like skin inflammation by inhibiting the VDR-mediated nuclear NF-κB and STAT signaling pathways. Mol Med Rep. 18:2733–2743. 2018.PubMed/NCBI View Article : Google Scholar

37 

Pivarcsi A, Meisgen F, Xu N, Ståhle M and Sonkoly E: Changes in the level of serum microRNAs in patients with psoriasis after antitumour necrosis factor-α therapy. Br J Dermatol. 169:563–570. 2013.PubMed/NCBI View Article : Google Scholar

38 

Loubaki L, Chabot D, Paré I, Drouin M and Bazin R: MiR-146a potentially promotes IVIg-mediated inhibition of TLR4 signaling in LPS-activated human monocytes. Immunol Lett. 185:64–73. 2017.PubMed/NCBI View Article : Google Scholar

39 

Liu AH, Wu YT and Wang YP: MicroRNA-129-5p inhibits the development of autoimmune encephalomyelitis-related epilepsy by targeting HMGB1 through the TLR4/NF-κB signaling pathway. Brain Res Bull. 132:139–149. 2017.PubMed/NCBI View Article : Google Scholar

40 

Nicolas JF: Psoriasis: How the epithelium influences the immune response: Keratinocytes, dendritic cells and T lymphocytes. Bull Acad Natl Med. 198:17–30. 2014.PubMed/NCBI(In French).

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ye Y, Wang P and Zhou F: miR‑489‑3p inhibits TLR4/NF‑κB signaling to prevent inflammation in psoriasis. Exp Ther Med 22: 744, 2021.
APA
Ye, Y., Wang, P., & Zhou, F. (2021). miR‑489‑3p inhibits TLR4/NF‑κB signaling to prevent inflammation in psoriasis. Experimental and Therapeutic Medicine, 22, 744. https://doi.org/10.3892/etm.2021.10176
MLA
Ye, Y., Wang, P., Zhou, F."miR‑489‑3p inhibits TLR4/NF‑κB signaling to prevent inflammation in psoriasis". Experimental and Therapeutic Medicine 22.1 (2021): 744.
Chicago
Ye, Y., Wang, P., Zhou, F."miR‑489‑3p inhibits TLR4/NF‑κB signaling to prevent inflammation in psoriasis". Experimental and Therapeutic Medicine 22, no. 1 (2021): 744. https://doi.org/10.3892/etm.2021.10176
Copy and paste a formatted citation
x
Spandidos Publications style
Ye Y, Wang P and Zhou F: miR‑489‑3p inhibits TLR4/NF‑κB signaling to prevent inflammation in psoriasis. Exp Ther Med 22: 744, 2021.
APA
Ye, Y., Wang, P., & Zhou, F. (2021). miR‑489‑3p inhibits TLR4/NF‑κB signaling to prevent inflammation in psoriasis. Experimental and Therapeutic Medicine, 22, 744. https://doi.org/10.3892/etm.2021.10176
MLA
Ye, Y., Wang, P., Zhou, F."miR‑489‑3p inhibits TLR4/NF‑κB signaling to prevent inflammation in psoriasis". Experimental and Therapeutic Medicine 22.1 (2021): 744.
Chicago
Ye, Y., Wang, P., Zhou, F."miR‑489‑3p inhibits TLR4/NF‑κB signaling to prevent inflammation in psoriasis". Experimental and Therapeutic Medicine 22, no. 1 (2021): 744. https://doi.org/10.3892/etm.2021.10176
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