Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

MicroRNA-27a Inhibits Cell Migration and Invasion of Fibroblast-Like Synoviocytes by Targeting Follistatin-Like Protein 1 in Rheumatoid Arthritis

  • Shi, Dong-liang (No. 1 Department of Osteopathy, Henan Province Hospital of TCM) ;
  • Shi, Gui-rong (Shangqiu Medical College) ;
  • Xie, Jing (No. 1 Department of Osteopathy, Henan Province Hospital of TCM) ;
  • Du, Xu-zhao (No. 1 Department of Osteopathy, Henan Province Hospital of TCM) ;
  • Yang, Hao (No. 1 Department of Osteopathy, Henan Province Hospital of TCM)
  • Received : 2016.04.20
  • Accepted : 2016.07.05
  • Published : 2016.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

Fibroblast-like synoviocytes (FLS) with aberrant expression of microRNA (miRNA) are critical pathogenic regulators in rheumatoid arthritis (RA). Previous studies have found that overexpression or silencing of miRNA can contribute to the development of miRNA-based therapeutics in arthritis models. In this study, we explored the effects of miR-27a on cell migration and invasion in cultured FLS from RA patients. We found that miR-27a was markedly downregulated in the serum, synovial tissue, and FLS of RA patients. Meanwhile, the expression of follistatin-like protein 1 (FSTL1) was upregulated, which suggests that FSTL1 plays a key role in RA development. The results of a Transwell assay showed that miR-27a inhibited FLS migration and invasion. However, miR-27a inhibition promoted the migration and invasion of FLS. In addition, the down-regulated expression of matrix metalloproteinases (MMP2, MMP9, and MMP13) and Rho family proteins (Rac1, Cdc42, and RhoA) was detected after treatment with miR-27a in RA-FLS by quantitative reverse transcription-PCR and western blot analysis. Then, a luciferase reporter assay validated that miR-27a targeted the 3-untranslated region (3'-UTR) of FSTL1. Moreover, miR-27a caused a significant decrease of FSTL1. In addition, the expression of TLR4 and $NF{\kappa}B$ was inhibited by miR-27a but increased by FSTL1 overexpression. In conclusion, we found that miR-27a inhibited cell migration and invasion of RA-FLS by targeting FSTL1 and restraining the $TLR4/NF{\kappa}B$ pathway.

Keywords

References

  1. Abeles, A.M., and Pillinger, M.H. (2006). The role of the synovial fibroblast in rheumatoid arthritis: cartilage destruction and the regulation of matrix metalloproteinases. Bull. NYU Hosp. Jt. Dis. 64, 20-24.
  2. Aletaha, D., Neogi, T., Silman, A.J., Funovits, J., Felson, D.T., Bingham, C.O., 3rd, Birnbaum, N.S., Burmester, G.R., Bykerk, V.P., Cohen, M.D., et al. (2010). 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 62, 2569-2581. https://doi.org/10.1002/art.27584
  3. Androulidaki, A., Iliopoulos, D., Arranz, A., Doxaki, C., Schworer, S., Zacharioudaki, V., Margioris, A.N., Tsichlis, P.N., and Tsatsanis, C. (2009). The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs. Immunity 31, 220-231. https://doi.org/10.1016/j.immuni.2009.06.024
  4. Bottini, N., and Firestein, G.S. (2013). Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors. Nat. Rev. Rheumatol. 9, 24-33. https://doi.org/10.1038/nrrheum.2012.190
  5. Chaly, Y., Marinov, A.D., Oxburgh, L., Bushnell, D.S., and Hirsch, R. (2012). FSTL1 promotes arthritis in mice by enhancing inflammatory cytokine/chemokine expression. Arthritis Rheum. 64, 1082-1088. https://doi.org/10.1002/art.33422
  6. Chen, W., Qi, J., Bao, G., Wang, T., Du, C.W., and Wang, M.D. (2015). Emerging role of microRNA-27a in human malignant glioma cell survival via targeting of prohibitin. Mol. Med. Rep. 12, 1515-1523. https://doi.org/10.3892/mmr.2015.3475
  7. Clutter, S.D., Wilson, D.C., Marinov, A.D., and Hirsch, R. (2009). Follistatin-like protein 1 promotes arthritis by up-regulating IFN-gamma. J. Immunol. 182, 234-239. https://doi.org/10.4049/jimmunol.182.1.234
  8. Ding, Q.H., Ji, X.W., Cheng, Y., Yu, Y.Q., Qi, Y.Y., and Wang, X.H. (2013). Inhibition of matrix metalloproteinases and inducible nitric oxide synthase by andrographolide in human osteoarthritic chondrocytes. Mod. Rheumatol. 23, 1124-1132. https://doi.org/10.3109/s10165-012-0807-6
  9. Duroux-Richard, I., Presumey, J., Courties, G., Gay, S., Gordeladze, J., Jorgensen, C., Kyburz, D., and Apparailly, F. (2011) MicroRNAs as new player in rheumatoid arthritis. Joint Bone Spine 78, 17-22. https://doi.org/10.1016/j.jbspin.2010.06.003
  10. Edris, B. (2011). A comparison of the Oligomap and TargetScan algorithms for miRNA target analysis. Bmi231.stanford.edu.
  11. Fassbender, H.G., and Simmling-Annefeld, M. (1983). The potential aggressiveness of synovial tissue in rheumatoid arthritis. J. Pathol. 139, 399-406. https://doi.org/10.1002/path.1711390314
  12. Fukuda, H., Nakamura, S., Chisaki, Y., Takada, T., Toda, Y., Murata, H., Itoh, K., Yano, Y., Takata, K., and Ashihara, E. (2016). Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression. Biochem. Biophys. Res. Commun. 471, 63-67. https://doi.org/10.1016/j.bbrc.2016.01.179
  13. Gallo, A., Tandon, M., Illei, G., and Alevizos, I. (2014). Discovery and validation of novel microRNAs in Sjogren's syndrome salivary glands. Clin. Exp. Rheumatol. 32, 761-762.
  14. Karouzakis, E., Gay, R.E., Gay, S., and Neidhart, M. (2009). Epigenetic control in rheumatoid arthritis synovial fibroblasts. Nat. Rev. Rheumatol. 5, 266-272. https://doi.org/10.1038/nrrheum.2009.55
  15. Lao, M., Shi, M., Zou, Y., Huang, M., Ye, Y., Qiu, Q., Xiao, Y., Zeng, S., Liang, L., Yang, X., et al. (2016). Protein inhibitor of activated STAT3 regulates migration, invasion, and activation of fibroblastlike synoviocytes in rheumatoid arthritis. J. Immunol. 196, 596-606. https://doi.org/10.4049/jimmunol.1403254
  16. Lefevre, S., Knedla, A., Tennie, C., Kampmann, A., Wunrau, C., Dinser, R., Korb, A., Schnaker, E. M., Tarner, I. H., Robbins, P.D., et al. (2009). Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat. Med. 15, 1414-1420. https://doi.org/10.1038/nm.2050
  17. Li, J., Wan, Y., Guo, Q., Zou, L., Zhang, J., Fang, Y., Fu, X., Liu, H., Lu, L., and Wu, Y. (2010). Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis. Arthritis Res. Ther. 12, R81. https://doi.org/10.1186/ar3006
  18. Li, G.F., Qin, Y.H., and Du, P.Q. (2015a). Andrographolide inhibits the migration, invasion and matrix metalloproteinase expression of rheumatoid arthritis fibroblast-like synoviocytes via inhibition of HIF-1alpha signaling. Life Sci. 136, 67-72. https://doi.org/10.1016/j.lfs.2015.06.019
  19. Li, W.Q., Yu, H.Y., Zhong, N.Z., Hou, L.J., Li, Y.M., He, J., Liu, H.M., Xia, C.Y., and Lu, Y.C. (2015b). miR27a suppresses the clonogenic growth and migration of human glioblastoma multiforme cells by targeting BTG2. Int. J. Oncol. 46, 1601-1608. https://doi.org/10.3892/ijo.2015.2843
  20. Li, X.Q., Lv, H.W., Wang, Z.L., Tan, W.F., Fang, B., and Ma, H. (2015c). MiR-27a ameliorates inflammatory damage to the blood-spinal cord barrier after spinal cord ischemia: reperfusion injury in rats by downregulating TICAM-2 of the TLR4 signaling pathway. J. Neuroinflammation 12, 25. https://doi.org/10.1186/s12974-015-0246-3
  21. Liang, L.Q., Huang, M.C., Qiu, Q., Xiao, Y.J., Sun, M.Y., Zhan, Z.P., Ye, Y.J., Fan, J.J., Yang, X.Y., and Xu, H.S. (2013) [Modulation of RhoA/Rho kinase on migration, invasion and proliferation of fibroblast like synoviocytes from patients with rheumatoid arthritis]. Zhonghua Yi Xue Za Zhi 93, 1345-1348.
  22. Liang, L., Huang, M., Xiao, Y., Zen, S., Lao, M., Zou, Y., Shi, M., Yang, X., and Xu, H. (2015). Inhibitory effects of niclosamide on inflammation and migration of fibroblast-like synoviocytes from patients with rheumatoid arthritis. Inflamm Res. 64, 225-233. https://doi.org/10.1007/s00011-015-0801-5
  23. Luo, X., Tsai, L.M., Shen, N., and Yu, D. (2010). Evidence for microRNA-mediated regulation in rheumatic diseases. Ann. Rheum. Dis. 69 Suppl 1, i30-36. https://doi.org/10.1136/ard.2009.117218
  24. Lv, Q., Zhu, X.Y., Xia, Y.F., Dai, Y., and Wei, Z.F. (2015). Tetrandrine inhibits migration and invasion of rheumatoid arthritis fibroblastlike synoviocytes through down-regulating the expressions of Rac1, Cdc42, and RhoA GTPases and activation of the PI3K/Akt and JNK signaling pathways. Chin J. Nat. Med. 13, 831-841.
  25. Lv, Y.N., Ou-Yang, A.J., and Fu, L.S. (2016). MicroRNA-27a negatively modulates the inflammatory response in lipopolysaccharide-stimulated microglia by targeting TLR4 and IRAK4. Cell Mol. Neurobiol. [Epub ahead of print]
  26. McInnes, I.B., and Schett, G. (2011). The pathogenesis of rheumatoid arthritis. N Engl. J. Med. 365, 2205-2219. https://doi.org/10.1056/NEJMra1004965
  27. Murakami, K., Tanaka, M., Usui, T., Kawabata, D., Shiomi, A., Iguchi-Hashimoto, M., Shimizu, M., Yukawa, N., Yoshifuji, H., Nojima, T., et al. (2012). Follistatin-related protein/follistatin-like 1 evokes an innate immune response via CD14 and toll-like receptor 4. FEBS Lett. 586, 319-324. https://doi.org/10.1016/j.febslet.2012.01.010
  28. Nakasa, T., Shibuya, H., Nagata, Y., Niimoto, T., and Ochi, M. (2011). The inhibitory effect of microRNA-146a expression on bone destruction in collagen-induced arthritis. Arthritis Rheum. 63, 1582-1590. https://doi.org/10.1002/art.30321
  29. O'Connell, R.M., Rao, D.S., and Baltimore, D. (2012). MicroRNA regulation of inflammatory responses. Annu. Rev. Immunol. 30, 295-312. https://doi.org/10.1146/annurev-immunol-020711-075013
  30. Okamoto, H., Shidara, K., Hoshi, D., and Kamatani, N. (2007). Antiarthritis effects of vitamin K(2) (menaquinone-4)--a new potential therapeutic strategy for rheumatoid arthritis. FEBS J. 274, 4588-4594. https://doi.org/10.1111/j.1742-4658.2007.05987.x
  31. Pan, W., Wang, H., Jianwei, R., and Ye, Z. (2014). MicroRNA-27a promotes proliferation, migration and invasion by targeting MAP2K4 in human osteosarcoma cells. Cell Physiol. Biochem. 33, 402-412. https://doi.org/10.1159/000356679
  32. Pratheeshkumar, P., and Kuttan, G. (2011). Andrographolide inhibits human umbilical vein endothelial cell invasion and migration by regulating MMP-2 and MMP-9 during angiogenesis. J. Environ. Pathol. Toxicol. Oncol. 30, 33-41. https://doi.org/10.1615/JEnvironPatholToxicolOncol.v30.i1.40
  33. Shibanuma, M., Mashimo, J., Mita, A., Kuroki, T., and Nose, K. (1993). Cloning from a mouse osteoblastic cell line of a set of transforming-growth-factor-beta 1-regulated genes, one of which seems to encode a follistatin-related polypeptide. Eur. J. Biochem. 217, 13-19. https://doi.org/10.1111/j.1432-1033.1993.tb18212.x
  34. Tardif, G., Hum, D., Pelletier, J.P., Duval, N., and Martel-Pelletier, J. (2009). Regulation of the IGFBP-5 and MMP-13 genes by the microRNAs miR-140 and miR-27a in human osteoarthritic chondrocytes. BMC Musculoskelet Disord. 10, 148. https://doi.org/10.1186/1471-2474-10-148
  35. Yang, S., and Yang, Y. (2015) Downregulation of microRNA221 decreases migration and invasion in fibroblastlike synoviocytes in rheumatoid arthritis. Mol. Med. Rep. 12, 2395-2401. https://doi.org/10.3892/mmr.2015.3642
  36. Yoshihara, Y., and Yamada, H. (2007). Matrix metalloproteinases and cartilage matrix degradation in rheumatoid arthritis. Clin. Calcium 17, 500-508.
  37. Yuan, H., Yang, P., Zhou, D., Gao, W., Qiu, Z., Fang, F., Ding, S., and Xiao, W. (2014). Knockdown of sphingosine kinase 1 inhibits the migration and invasion of human rheumatoid arthritis fibroblast-like synoviocytes by down-regulating the PI3K/AKT activation and MMP-2/9 production in vitro. Mol. Biol. Rep. 41, 5157-5165. https://doi.org/10.1007/s11033-014-3382-4
  38. Zhang, X.H., Xu, X.X., and Xu, T. (2015). Ginsenoside Ro suppresses interleukin-1beta-induced apoptosis and inflammation in rat chondrocytes by inhibiting NF-kappaB. Chin J. Nat. Med. 13, 283-289.
  39. Zhang, S., Ma, C., Pang, H., Zeng, F., Cheng, L., Fang, B., Ma, J., Shi, Y., Hong, H., Chen, J., et al. (2016). Arsenic trioxide suppresses cell growth and migration via inhibition of miR-27a in breast cancer cells. Biochem. Biophys. Res. Commun. 469, 55-61. https://doi.org/10.1016/j.bbrc.2015.11.071
  40. Zhao, W., Zhang, C., Shi, M., Zhang, J., Li, M., Xue, X., Zhang, Z., Shu, Z., Zhu, J., Mu, N., et al. (2014). The discoidin domain receptor 2/annexin A2/matrix metalloproteinase 13 loop promotes joint destruction in arthritis through promoting migration and invasion of fibroblast-like synoviocytes. Arthritis Rheumatol. 66, 2355-2367. https://doi.org/10.1002/art.38696

Cited by

  1. The influence of fibroblast on the arachnoid leptomeningeal cells in vitro vol.1657, 2017, https://doi.org/10.1016/j.brainres.2016.12.004
  2. Fine particulate matter exposure induces cell cycle arrest and inhibits migration and invasion of human extravillous trophoblast, as determined by an iTRAQ-based quantitative proteomics strategy 2017, https://doi.org/10.1016/j.reprotox.2017.08.014
  3. TLR-4/miRNA-32-5p/FSTL1 signaling regulates mycobacterial survival and inflammatory responses in Mycobacterium tuberculosis -infected macrophages vol.352, pp.2, 2017, https://doi.org/10.1016/j.yexcr.2017.02.025
  4. LncRNA ZFAS1 promotes cell migration and invasion of fibroblast-like synoviocytes by suppression of miR-27a in rheumatoid arthritis 2017, https://doi.org/10.1007/s13577-017-0179-5
  5. Plasma MicroRNA Profiles in Patients with Early Rheumatoid Arthritis Responding to Adalimumab plus Methotrexate vs Methotrexate Alone: A Placebo-controlled Clinical Trial vol.45, pp.1, 2017, https://doi.org/10.3899/jrheum.170266
  6. Epigenetics of inflammatory arthritis vol.30, pp.2, 2018, https://doi.org/10.1097/BOR.0000000000000471
  7. MicroRNA-27a alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis through modulating TLR4/MyD88/NF-κB pathway vol.17, pp.16, 2018, https://doi.org/10.1080/15384101.2018.1509635
  8. Deficiency of Follistatin-Like Protein 1 Accelerates the Growth of Breast Cancer Cells at Lung Metastatic Sites vol.21, pp.3, 2018, https://doi.org/10.4048/jbc.2018.21.e43
  9. The Micro-RNA Expression Profiles of Autoimmune Arthritis Reveal Novel Biomarkers of the Disease and Therapeutic Response vol.19, pp.8, 2018, https://doi.org/10.3390/ijms19082293
  10. Inhibition of microRNA-9-5p Protects against Cardiac Remodeling following Myocardial Infarction in Mice pp.1557-7422, 2019, https://doi.org/10.1089/hum.2018.059
  11. Follistatin-like 1 in development and human diseases vol.75, pp.13, 2018, https://doi.org/10.1007/s00018-018-2805-0
  12. An OMIC biomarker detection algorithm TriVote and its application in methylomic biomarker detection vol.10, pp.4, 2018, https://doi.org/10.2217/epi-2017-0097
  13. The Effects of MicroRNAs on Key Signalling Pathways and Epigenetic Modification in Fibroblast-Like Synoviocytes of Rheumatoid Arthritis vol.2018, pp.1466-1861, 2018, https://doi.org/10.1155/2018/9013124
  14. The relevance of microRNA in post-infarction left ventricular remodelling and heart failure pp.1573-7322, 2019, https://doi.org/10.1007/s10741-019-09770-9
  15. 电针对佐剂性关节炎大鼠滑膜组织c-IAP1 mRNA 和c-IAP2 mRNA 的影响 vol.17, pp.1, 2019, https://doi.org/10.1007/s11726-019-1088-9
  16. FSTL1 Promotes Metastasis and Chemoresistance in Esophageal Squamous Cell Carcinoma through NFκB–BMP Signaling Cross-talk vol.77, pp.21, 2016, https://doi.org/10.1158/0008-5472.can-17-1411
  17. Monocyte-related biomarkers of rheumatoid arthritis development in undifferentiated arthritis patients – a pilot study vol.56, pp.1, 2016, https://doi.org/10.5114/reum.2018.74742
  18. Plasma MicroRNAs in Established Rheumatoid Arthritis Relate to Adiposity and Altered Plasma and Skeletal Muscle Cytokine and Metabolic Profiles vol.10, pp.None, 2019, https://doi.org/10.3389/fimmu.2019.01475
  19. The function of ncRNAs in rheumatic diseases vol.11, pp.7, 2019, https://doi.org/10.2217/epi-2018-0135
  20. MiRNA-506 inhibits rheumatoid arthritis fibroblast-like synoviocytes proliferation and induces apoptosis by targetting TLR4 vol.39, pp.5, 2016, https://doi.org/10.1042/bsr20182500
  21. miR-22-5p and miR-29a-5p Are Reliable Reference Genes for Analyzing Extracellular Vesicle-Associated miRNAs in Adipose-Derived Mesenchymal Stem Cells and Are Stable under Inflammatory Priming Mimickin vol.15, pp.5, 2016, https://doi.org/10.1007/s12015-019-09899-y
  22. Structural and functional study of FK domain of Fstl1 vol.28, pp.10, 2016, https://doi.org/10.1002/pro.3696
  23. MicroRNA-155 Participates in the Expression of LSD1 and Proinflammatory Cytokines in Rheumatoid Synovial Cells vol.2020, pp.None, 2016, https://doi.org/10.1155/2020/4092762
  24. Emerging Concepts and Challenges in Rheumatoid Arthritis Gene Therapy vol.8, pp.1, 2016, https://doi.org/10.3390/biomedicines8010009
  25. Periplocin induces apoptosis and inhibits inflammation in rheumatoid arthritis fibroblast‐like synoviocytes via nuclear factor kappa B pathway vol.72, pp.9, 2020, https://doi.org/10.1002/iub.2328
  26. MicroRNA-137-mediated inhibition of lysine-specific demethylase-1 prevents against rheumatoid arthritis in an association with the REST/mTOR axis vol.17, pp.None, 2016, https://doi.org/10.1177/17448069211041847
  27. Circ_0088194 Promotes the Invasion and Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes via the miR-766-3p/MMP2 Axis vol.12, pp.None, 2016, https://doi.org/10.3389/fimmu.2021.628654
  28. Mechanism of miR-218-5p in autophagy, apoptosis and oxidative stress in rheumatoid arthritis synovial fibroblasts is mediated by KLF9 and JAK/STAT3 pathways vol.69, pp.4, 2016, https://doi.org/10.1136/jim-2020-001437
  29. Signalling and putative therapeutic molecules on the regulation of synoviocyte signalling in rheumatoid arthritis vol.10, pp.4, 2021, https://doi.org/10.1302/2046-3758.104.bjr-2020-0331.r1
  30. miR-200c-3p Regulates Epitelial-to-Mesenchymal Transition in Epicardial Mesothelial Cells by Targeting Epicardial Follistatin-Related Protein 1 vol.22, pp.9, 2016, https://doi.org/10.3390/ijms22094971
  31. miR-216a-5p Suppresses the Proliferation, Invasion and Migration of Fibroblast-Like Synoviocyte in Rheumatoid Arthritis by Targeting Zinc Finger and BTB Domain-Containing Protein 2 (ZBTB2) vol.11, pp.5, 2021, https://doi.org/10.1166/jbt.2021.2589
  32. The Expression of Non-Coding RNAs and Their Target Molecules in Rheumatoid Arthritis: A Molecular Basis for Rheumatoid Pathogenesis and Its Potential Clinical Applications vol.22, pp.11, 2016, https://doi.org/10.3390/ijms22115689
  33. An Analysis of Mechanisms for Cellular Uptake of miRNAs to Enhance Drug Delivery and Efficacy in Cancer Chemoresistance vol.7, pp.2, 2021, https://doi.org/10.3390/ncrna7020027
  34. ZFAS1 knockdown inhibits fibroblast‑like synoviocyte proliferation, migration, invasion and inflammation, and promotes apoptosis via miR‑3926/FSTL1 in rheumatoid arthritis vol.22, pp.3, 2016, https://doi.org/10.3892/etm.2021.10346
  35. TNF‐α induces up‐regulation of MicroRNA‐27a via the P38 signalling pathway, which inhibits intervertebral disc degeneration by targeting FSTL1 vol.25, pp.15, 2016, https://doi.org/10.1111/jcmm.16745
  36. PLD1 knockdown reduces metastasis and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis by modulating NF-κB and Wnt/β-catenin pathways vol.54, pp.7, 2021, https://doi.org/10.1080/08916934.2021.1963957
  37. Rho GTPase signaling in rheumatic diseases vol.25, pp.1, 2016, https://doi.org/10.1016/j.isci.2021.103620