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TUG1 knockdown promoted viability and inhibited apoptosis and cartilage ECM degradation in chondrocytes via the miR‑17‑5p/FUT1 pathway in osteoarthritis

  • Authors:
    • Zhichao Li
    • Jin Wang
    • Jing Yang
  • View Affiliations / Copyright

    Affiliations: Department of Hand, Foot and Vascular Surgery, Hanyang Hospital, Wuhan University of Science and Technology, Wuhan, Hubei 430050, P.R. China, Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, Hubei 430060, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 154
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    Published online on: October 6, 2020
       https://doi.org/10.3892/etm.2020.9283
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Abstract

Osteoarthritis (OA) is a degenerative disease characterized by cartilage destruction. Previous research has demonstrated that long non‑coding RNAs serve a role in OA progression. The current study aimed to determine the function and mechanism of taurine upregulated gene (TUG) 1 in OA. The results of reverse transcription quantitative PCR revealed that TUG1 was elevated in OA cartilage tissues and interleukin (IL)‑1β‑induced chondrocytes. Cell Counting kit‑8 and flow cytometry analysis revealed that TUG1 knockdown promoted cell viability and inhibited cell apoptosis. Furthermore, matrix metalloprotein (MMP) 13, collagen II and aggrecan expression was determined by western blotting, of which the results demonstrated that TUG1 knockdown significantly decreased MMP13 expression and increased collagen II and aggrecan expression in IL‑1β‑stimulated chondrocytes, indicating that extracellular matrix (ECM) damage was inhibited. Additionally, using bioinformatics analysis, dual‑luciferase reporter and RNA immunoprecipitation assays, TUG1 was revealed to upregulate fucosyltransferase (FUT) 1 by targeting miR‑17‑5p. Furthermore, miR‑17‑5p was downregulated and FUT1 upregulated in OA cartilage tissues and IL‑1β‑induced chondrocytes. TUG1 overexpression reversed the aforementioned effects on cell viability, cell apoptosis and ECM degradation mediated by miR‑17‑5p in IL‑1β‑activated chondrocytes. Additionally, the effects of FUT1 knockdown on cell viability, apoptosis and ECM degradation mediated by FUT1 knockdown were reversed by miR‑17‑5p inhibition. In conclusion, TUG1 knockdown inhibited OA progression by downregulating FUT1 via miR‑17‑5p.
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1 

Arden N and Nevitt MC: Osteoarthritis: Epidemiology. Best Pract Res Clin Rheumatol. 20:3–25. 2006.PubMed/NCBI View Article : Google Scholar

2 

Michael JW, Schlüter-Brust KU and Eysel P: The epidemiology, etiology, diagnosis, and treatment of osteoarthritis of the knee. Dtsch Arztebl Int. 107:152–162. 2010.PubMed/NCBI View Article : Google Scholar

3 

Rahmati M, Nalesso G, Mobasheri A and Mozafari M: Aging and osteoarthritis: Central role of the extracellular matrix. Ageing Res Rev. 40:20–30. 2017.PubMed/NCBI View Article : Google Scholar

4 

Van der Kraan P, Buma P, Van Kuppevelt T and Van Den Berg W: Interaction of chondrocytes, extracellular matrix and growth factors: Relevance for articular cartilage tissue engineering. Osteoarthritis Cartilage. 10:631–637. 2002.PubMed/NCBI View Article : Google Scholar

5 

Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, Bridgett L, Williams S, Guillemin F, Hill CL, et al: The global burden of hip and knee osteoarthritis: Estimates from the global burden of disease 2010 study. Ann Rheum Dis. 73:1323–1330. 2014.PubMed/NCBI View Article : Google Scholar

6 

Johnsson P, Lipovich L, Grandér D and Morris KV: Evolutionary conservation of long non-coding RNAs; sequence, structure, function. Biochim Biophys Acta. 1840:1063–1071. 2014.PubMed/NCBI View Article : Google Scholar

7 

Mercer TR, Dinger ME and Mattick JS: Long non-coding RNAs: Insights into functions. Nat Rev Genet. 10:155–159. 2009.PubMed/NCBI View Article : Google Scholar

8 

Niu Y, Ma F, Huang W, Fang S, Li M, Wei T and Guo L: Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2. Mol Cancer. 16(5)2017.PubMed/NCBI View Article : Google Scholar

9 

Huang MD, Chen WM, Qi FZ, Sun M, Xu TP, Ma P and Shu YQ: Long non-coding RNA TUG1 is up-regulated in hepatocellular carcinoma and promotes cell growth and apoptosis by epigenetically silencing of KLF2. Mol Cancer. 14(165)2015.PubMed/NCBI View Article : Google Scholar

10 

Hu J, Wang Z, Shan Y, Pan Y, Ma J and Jia L: Long non-coding RNA HOTAIR promotes osteoarthritis progression via miR-17-5p/FUT2/β-catenin axis. Cell Death Dis. 9(711)2018.PubMed/NCBI View Article : Google Scholar

11 

Chen K, Zhu H, Zheng M-Q and Dong QR: lncRNA MEG3 inhibits the degradation of the extracellular matrix of chondrocytes in osteoarthritis via targeting miR-93/TGFBR2 Axis. Cartilage: Jun 28, 2019 (Epub ahead of print). doi: 10.1177/1947603519855759.

12 

Li L, Lv G, Wang B and Kuang L: The role of lncRNA XIST/miR-211 axis in modulating the proliferation and apoptosis of osteoarthritis chondrocytes through CXCR4 and MAPK signaling. Biochem Biophys Res Commun. 503:2555–2562. 2018.PubMed/NCBI View Article : Google Scholar

13 

He L and Hannon GJ: MicroRNAs: Small RNAs with a big role in gene regulation. Nat Rev Genet. 5:522–531. 2004.PubMed/NCBI View Article : Google Scholar

14 

Huang J, Zhao L, Fan Y, Liao L, Ma PX, Xiao G and Chen D: The microRNAs miR-204 and miR-211 maintain joint homeostasis and protect against osteoarthritis progression. Nat Commun. 10(2876)2019.PubMed/NCBI View Article : Google Scholar

15 

Meng F, Li Z, Zhang Z, Yang Z, Kang Y, Zhao X, Long D, Hu S, Gu M, He S, et al: MicroRNA-193b-3p regulates chondrogenesis and chondrocyte metabolism by targeting HDAC3. Theranostics. 8:2862–2883. 2018.PubMed/NCBI View Article : Google Scholar

16 

Cai C, Min S, Yan B, Liu W, Yang X, Li L, Wang T and Jin A: miR-27a promotes the autophagy and apoptosis of IL-1β treated-articular chondrocytes in osteoarthritis through PI3K/AKT/mTOR signaling. Aging (Albany NY). 11:6371–6384. 2019.PubMed/NCBI View Article : Google Scholar

17 

Yang B, Kang X, Xing Y, Dou C, Kang F, Li J, Quan Y and Dong S: Effect of microRNA-145 on IL-1β-induced cartilage degradation in human chondrocytes. FEBS Lett. 588:2344–2352. 2014.PubMed/NCBI View Article : Google Scholar

18 

Pilyugin M and Irminger-Finger I: Long non-coding RNA and microRNAs might act in regulating the expression of BARD1 mRNAs. Int J Biochem Cell Biol. 54:356–367. 2014.PubMed/NCBI View Article : Google Scholar

19 

Mizuochi T, Taniguchi T, Shimizu A and Kobata A: Structural and numerical variations of the carbohydrate moiety of immunoglobulin G. J Immunol. 129:2016–2020. 1982.PubMed/NCBI

20 

Hu J, Wang Z, Pan Y, Ma J, Miao X, Qi X, Zhou H and Jia L: miR-26a and miR-26b mediate osteoarthritis progression by targeting FUT4 via NF-κB signaling pathway. Int J Biochem Cell Biol. 94:79–88. 2018.PubMed/NCBI View Article : Google Scholar

21 

Ma B, Simala-Grant JL and Taylor DE: Fucosylation in prokaryotes and eukaryotes. Glycobiology. 16:158R–184R. 2006.PubMed/NCBI 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.PubMed/NCBI View Article : Google Scholar

23 

Lu J, Deng ZH, Li YS and Lei GH: Long noncoding RNAs in osteoarthritis. Joint Bone Spine. 84:553–556. 2017.PubMed/NCBI View Article : Google Scholar

24 

Xing D, Liang Jq, Li Y, Lu J, Jia Hb, Xu Ly and Ma Xl: Identification of long noncoding RNA associated with osteoarthritis in humans. Orthop Surg. 6:288–293. 2014.PubMed/NCBI View Article : Google Scholar

25 

Aida Y, Maeno M, Suzuki N, Shiratsuchi H, Motohashi M and Matsumura H: The effect of IL-1beta on the expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in human chondrocytes. Life Sci. 77:3210–3221. 2005.PubMed/NCBI View Article : Google Scholar

26 

Daheshia M and Yao JQ: The interleukin 1beta pathway in the pathogenesis of osteoarthritis. J Rheumatol. 35:2306–2312. 2008.PubMed/NCBI View Article : Google Scholar

27 

Lopez-Armada MJ, Carames B, Lires-Dean M, Cillero-Pastor B, Ruiz-Romero C, Galdo F and Blanco FJ: Cytokines, tumor necrosis factor-alpha and interleukin-1beta, differentially regulate apoptosis in osteoarthritis cultured human chondrocytes. Osteoarthritis Cartilage. 14:660–669. 2006.PubMed/NCBI View Article : Google Scholar

28 

Takahashi A, de Andrés MC, Hashimoto K, Itoi E, Otero M, Goldring MB and Oreffo ROC: DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes. Sci Rep. 7(7771)2017.PubMed/NCBI View Article : Google Scholar

29 

Larkin J, Lohr TA, Elefante L, Shearin J, Matico R, Su JL, Xue Y, Liu F, Genell C, Miller RE, et al: Translational development of an ADAMTS-5 antibody for osteoarthritis disease modification. Osteoarthritis Cartilage. 23:1254–1266. 2015.PubMed/NCBI View Article : Google Scholar

30 

Liang Z and Ren C: Emodin attenuates apoptosis and inflammation induced by LPS through up-regulating lncRNA TUG1 in murine chondrogenic ATDC5 cells. Biomed Pharmacothery. 103:897–902. 2018.PubMed/NCBI View Article : Google Scholar

31 

Tang LP, Ding JB, Liu ZH and Zhou GJ: lncRNA TUG1 promotes osteoarthritis-induced degradation of chondrocyte extracellular matrix via miR-195/MMP-13 axis. Euro Rev Med Pharmacol Sci. 22:8574–8581. 2018.PubMed/NCBI View Article : Google Scholar

32 

Li J, Lai Y, Ma J, Liu Y, Bi J, Zhang L, Chen L, Yao C, Lv W, Chang G, et al: miR-17-5p suppresses cell proliferation and invasion by targeting ETV1 in triple-negative breast cancer. BMC Cancer. 17(745)2017.PubMed/NCBI View Article : Google Scholar

33 

Yang F, Yin Y, Wang F, Wang Y, Zhang L, Tang Y and Sun S: miR-17-5p Promotes migration of human hepatocellular carcinoma cells through the p38 mitogen-activated protein kinase-heat shock protein 27 pathway. Hepatology. 51:1614–1623. 2010.PubMed/NCBI View Article : Google Scholar

34 

Ma Y, Zhang P, Wang F, Zhang H, Yang Y, Shi C, Xia Y, Peng J, Liu W, Yang Z and Qin H: Elevated oncofoetal miR-17-5p expression regulates colorectal cancer progression by repressing its target gene P130. Nat Commun. 3(1291)2012.PubMed/NCBI View Article : Google Scholar

35 

Lai TY, Chen IJ, Lin RJ, Liao GS, Yeo HL, Ho CL, Wu JC, Chang NC, Lee AC and Alice LY: Fucosyltransferase 1 and 2 play pivotal roles in breast cancer cells. Cell Death Discov. 5(74)2019.PubMed/NCBI View Article : Google Scholar

36 

Kawai S, Kato S, Imai H, Okada Y and Ishioka C: Suppression of FUT1 attenuates cell proliferation in the HER2-overexpressing cancer cell line NCI-N87. Oncol Rep. 29:13–20. 2013.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Li Z, Wang J and Yang J: TUG1 knockdown promoted viability and inhibited apoptosis and cartilage ECM degradation in chondrocytes via the miR‑17‑5p/FUT1 pathway in osteoarthritis. Exp Ther Med 20: 154, 2020.
APA
Li, Z., Wang, J., & Yang, J. (2020). TUG1 knockdown promoted viability and inhibited apoptosis and cartilage ECM degradation in chondrocytes via the miR‑17‑5p/FUT1 pathway in osteoarthritis. Experimental and Therapeutic Medicine, 20, 154. https://doi.org/10.3892/etm.2020.9283
MLA
Li, Z., Wang, J., Yang, J."TUG1 knockdown promoted viability and inhibited apoptosis and cartilage ECM degradation in chondrocytes via the miR‑17‑5p/FUT1 pathway in osteoarthritis". Experimental and Therapeutic Medicine 20.6 (2020): 154.
Chicago
Li, Z., Wang, J., Yang, J."TUG1 knockdown promoted viability and inhibited apoptosis and cartilage ECM degradation in chondrocytes via the miR‑17‑5p/FUT1 pathway in osteoarthritis". Experimental and Therapeutic Medicine 20, no. 6 (2020): 154. https://doi.org/10.3892/etm.2020.9283
Copy and paste a formatted citation
x
Spandidos Publications style
Li Z, Wang J and Yang J: TUG1 knockdown promoted viability and inhibited apoptosis and cartilage ECM degradation in chondrocytes via the miR‑17‑5p/FUT1 pathway in osteoarthritis. Exp Ther Med 20: 154, 2020.
APA
Li, Z., Wang, J., & Yang, J. (2020). TUG1 knockdown promoted viability and inhibited apoptosis and cartilage ECM degradation in chondrocytes via the miR‑17‑5p/FUT1 pathway in osteoarthritis. Experimental and Therapeutic Medicine, 20, 154. https://doi.org/10.3892/etm.2020.9283
MLA
Li, Z., Wang, J., Yang, J."TUG1 knockdown promoted viability and inhibited apoptosis and cartilage ECM degradation in chondrocytes via the miR‑17‑5p/FUT1 pathway in osteoarthritis". Experimental and Therapeutic Medicine 20.6 (2020): 154.
Chicago
Li, Z., Wang, J., Yang, J."TUG1 knockdown promoted viability and inhibited apoptosis and cartilage ECM degradation in chondrocytes via the miR‑17‑5p/FUT1 pathway in osteoarthritis". Experimental and Therapeutic Medicine 20, no. 6 (2020): 154. https://doi.org/10.3892/etm.2020.9283
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