MicroRNA-155 Participates in the Expression of LSD1 and Proinflammatory Cytokines in Rheumatoid Synovial Cells
Ziliang Yu
Department of Orthopaedics, Affiliated Hospital 2 of Nantong University, Nantong University, Nantong 226001, China ntu.edu.cn
Search for more papers by this authorHao Liu
School of Clinical Medicine, Nanjing Medical University, Nanjing 211166, China njmu.edu.cn
Search for more papers by this authorJianbo Fan
Department of Orthopaedics, Affiliated Hospital 2 of Nantong University, Nantong University, Nantong 226001, China ntu.edu.cn
Search for more papers by this authorFeihu Chen
Department of Orthopaedics, Affiliated Hospital 2 of Nantong University, Nantong University, Nantong 226001, China ntu.edu.cn
Search for more papers by this authorCorresponding Author
Wei Liu
Department of Orthopaedics, Affiliated Hospital 2 of Nantong University, Nantong University, Nantong 226001, China ntu.edu.cn
Search for more papers by this authorZiliang Yu
Department of Orthopaedics, Affiliated Hospital 2 of Nantong University, Nantong University, Nantong 226001, China ntu.edu.cn
Search for more papers by this authorHao Liu
School of Clinical Medicine, Nanjing Medical University, Nanjing 211166, China njmu.edu.cn
Search for more papers by this authorJianbo Fan
Department of Orthopaedics, Affiliated Hospital 2 of Nantong University, Nantong University, Nantong 226001, China ntu.edu.cn
Search for more papers by this authorFeihu Chen
Department of Orthopaedics, Affiliated Hospital 2 of Nantong University, Nantong University, Nantong 226001, China ntu.edu.cn
Search for more papers by this authorCorresponding Author
Wei Liu
Department of Orthopaedics, Affiliated Hospital 2 of Nantong University, Nantong University, Nantong 226001, China ntu.edu.cn
Search for more papers by this authorAbstract
MicroRNA-155 (miRNA-155) is abundant in fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). Lysine-specific demethylase 1 (LSD1) has been found that it can ameliorate the severity of RA. Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 are key proinflammatory cytokines implicated in the pathogenesis of RA. In our study, we investigated whether miRNA-155 participates in the expression of LSD1 and proinflammatory cytokines in rheumatoid synovial cells. First of all, flow cytometry and cell counting kit-8 analysis were employed to explore the apoptosis and proliferation of FLS, respectively. Subsequently, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to probe into the level of miRNA-155 in FLS when stimulated by miRNA-155 molecules. Moreover, RT-qPCR was used to explore the relative LSD1 miRNA expression in FLS when stimulated by miRNA-155 molecules, and Western blot and immunofluorescence assay were applied to probe into the expression level of LSD1. Finally, enzyme-linked immunosorbent assay was employed to analyze the secreting level of proinflammatory cytokines in FLS when stimulated by miRNA-155 molecules. RA-FLS showed a higher apoptosis rate than normal FLS. The cell proliferation of both HFLS and MH7A cells was promoted by miRNA-155 upregulation. Meanwhile, the expression of LSD1 and proinflammatory cytokines in the FLS of RA was also changed by miRNA-155 regulation. In conclusion, miRNA-155 participates in the expression of LSD1 and proinflammatory cytokines in rheumatoid synovial cells. These findings imply a potential function and interaction of miRNA-155 and LSD1.
Conflicts of Interest
The authors declare that there is no conflict of interest regarding the publication of this paper.
Open Research
Data Availability
The data used to support the findings of this study are available from the corresponding author upon request.
References
- 1 Fazal S. A., Khan M., Nishi S. E., Alam F., Zarin N., Bari M. T., and Ashraf G. M., A clinical update and global economic burden of rheumatoid arthritis, Endocrine, Metabolic & Immune Disorders Drug Targets. (2018) 18, no. 2, 98–109, https://doi.org/10.2174/1871530317666171114122417, 2-s2.0-85043307944.
- 2 van der Woude D. and van der Helm-van Mil A. H. M., Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis, Best Practice & Research. Clinical Rheumatology. (2018) 32, no. 2, 174–187, https://doi.org/10.1016/j.berh.2018.10.005, 2-s2.0-85056605073, 30527425.
- 3 Smolen J. S., Aletaha D., and McInnes I. B., Rheumatoid arthritis, Lancet. (2016) 388, no. 10055, 2023–2038, https://doi.org/10.1016/S0140-6736(16)30173-8, 2-s2.0-84964773927.
- 4 McInnes I. B. and Schett G., The pathogenesis of rheumatoid arthritis, The New England Journal of Medicine. (2011) 365, no. 23, 2205–2219, https://doi.org/10.1056/NEJMra1004965, 2-s2.0-84855172814, 22150039.
- 5 Noss E. H. and Brenner M. B., The role and therapeutic implications of fibroblast-like synoviocytes in inflammation and cartilage erosion in rheumatoid arthritis, Immunological Reviews. (2008) 223, no. 1, 252–270, https://doi.org/10.1111/j.1600-065X.2008.00648.x, 2-s2.0-47249086030.
- 6 McInnes I. B., Buckley C. D., and Isaacs J. D., Cytokines in rheumatoid arthritis - shaping the immunological landscape, Nature Reviews Rheumatology. (2016) 12, no. 1, 63–68, https://doi.org/10.1038/nrrheum.2015.171, 2-s2.0-84954197348, 26656659.
- 7 Alam J., Jantan I., and Bukhari S. N. A., Rheumatoid arthritis: recent advances on its etiology, role of cytokines and pharmacotherapy, Biomedicine & Pharmacotherapy. (2017) 92, 615–633, https://doi.org/10.1016/j.biopha.2017.05.055, 2-s2.0-85020029836, 28582758.
- 8 Bek S., Bojesen A. B., Nielsen J. V., Sode J., Bank S., Vogel U., and Andersen V., Systematic review and meta-analysis: pharmacogenetics of anti-TNF treatment response in rheumatoid arthritis, The Pharmacogenomics Journal. (2017) 17, no. 5, 403–411, https://doi.org/10.1038/tpj.2017.26, 2-s2.0-85029746427, 28607508.
- 9 Narazaki M., Tanaka T., and Kishimoto T., The role and therapeutic targeting of IL-6 in rheumatoid arthritis, Expert Review of Clinical Immunology. (2017) 13, no. 6, 535–551, https://doi.org/10.1080/1744666X.2017.1295850, 2-s2.0-85019241339, 28494214.
- 10 Zhai K. F., Duan H., Cui C. Y., Cao Y. Y., Si J. L., Yang H. J., Wang Y. C., Cao W. G., Gao G. Z., and Wei Z. J., Liquiritin from Glycyrrhiza uralensis attenuating rheumatoid arthritis via reducing inflammation, suppressing angiogenesis, and inhibiting MAPK signaling pathway, Journal of Agricultural and Food Chemistry. (2019) 67, no. 10, 2856–2864, https://doi.org/10.1021/acs.jafc.9b00185, 2-s2.0-85062542457, 30785275.
- 11 Qiu H., Wu H., Chan V., Lau C. S., and Lu Q., Transcriptional and epigenetic regulation of follicular T-helper cells and their role in autoimmunity, Autoimmunity. (2017) 50, no. 2, 71–81, https://doi.org/10.1080/08916934.2017.1284821, 2-s2.0-85013436158, 28263097.
- 12 Meng M., Liu H., Chen S., Zhao H., Gao X., Zhang J., and Chen D., Methylation of H3K27 and H3K4 in key gene promoter regions of thymus in RA mice is involved in the abnormal development and differentiation of iNKT cells, Immunogenetics. (2019) 71, no. 7, 489–499, https://doi.org/10.1007/s00251-019-01124-x, 2-s2.0-85069163906.
- 13 Shi Y., Lan F., Matson C., Mulligan P., Whetstine J. R., Cole P. A., Casero R. A., and Shi Y., Histone demethylation mediated by the nuclear amine oxidase homolog LSD1, Cell. (2004) 119, no. 7, 941–953, https://doi.org/10.1016/j.cell.2004.12.012, 2-s2.0-11144332565, 15620353.
- 14 Huang Y., Vasilatos S. N., Boric L., Shaw P. G., and Davidson N. E., Inhibitors of histone demethylation and histone deacetylation cooperate in regulating gene expression and inhibiting growth in human breast cancer cells, Breast Cancer Research and Treatment. (2012) 131, no. 3, 777–789, https://doi.org/10.1007/s10549-011-1480-8, 2-s2.0-84856230241.
- 15 Liu W., Fan J.-B., Xu D.-W., Zhu X.-H., Yi H., Cui S.-Y., Zhang J., and Cui Z.-M., Knockdown of LSD1 ameliorates the severity of rheumatoid arthritis and decreases the function of CD4 T cells in mouse models, International Journal of Clinical and Experimental Pathology. (2018) 11, no. 1, 333–341.
- 16 Faraoni I., Antonetti F. R., Cardone J., and Bonmassar E., miR-155 gene: a typical multifunctional microRNA, Biochimica et Biophysica Acta. (2009) 1792, no. 6, 497–505, https://doi.org/10.1016/j.bbadis.2009.02.013, 2-s2.0-67349083526, 19268705.
- 17 Yan Q., Chen J., Li W., Bao C., and Fu Q., Targeting miR-155 to treat experimental scleroderma, Scientific Reports. (2016) 6, no. 1, https://doi.org/10.1038/srep20314, 2-s2.0-84957541803.
- 18 Artlett C. M., Sassi-Gaha S., Hope J. L., Feghali-Bostwick C. A., and Katsikis P. D., Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis, Arthritis Research & Therapy. (2017) 19, no. 1, https://doi.org/10.1186/s13075-017-1331-z, 2-s2.0-85021165379.
- 19 Hayashi T., Kaneda T., Toyama Y., Kumegawa M., and Hakeda Y., Regulation of receptor activator of NF-kappa B ligand-induced osteoclastogenesis by endogenous interferon-beta (INF-beta ) and suppressors of cytokine signaling (SOCS). The possible counteracting role of SOCSs- in IFN-beta-inhibited osteoclast formation, The Journal of Biological Chemistry. (2002) 277, no. 31, 27880–27886, https://doi.org/10.1074/jbc.M203836200, 2-s2.0-0037008742, 12023971.
- 20 Mann M., Barad O., Agami R., Geiger B., and Hornstein E., miRNA-based mechanism for the commitment of multipotent progenitors to a single cellular fate, Proceedings of the National Academy of Sciences of the United States of America. (2010) 107, no. 36, 15804–15809, https://doi.org/10.1073/pnas.0915022107, 2-s2.0-77957664009, 20720163.
- 21 Zhang J., Zhao H., Chen J., Xia B., Jin Y., Wei W., Shen J., and Huang Y., Interferon-β-induced miR-155 inhibits osteoclast differentiation by targeting SOCS1 and MITF, FEBS Letters. (2012) 586, no. 19, 3255–3262, https://doi.org/10.1016/j.febslet.2012.06.047, 2-s2.0-84866596352.
- 22 Blüml S., Bonelli M., Niederreiter B., Puchner A., Mayr G., Hayer S., Koenders M. I., van den Berg W. B., Smolen J., and Redlich K., Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice, Arthritis and Rheumatism. (2011) 63, no. 5, 1281–1288, https://doi.org/10.1002/art.30281, 2-s2.0-79955561084, 21321928.
- 23 Daniunaite K., Dubikaityte M., Gibas P., Bakavicius A., Rimantas Lazutka J., Ulys A., Jankevicius F., and Jarmalaite S., Clinical significance of miRNA host gene promoter methylation in prostate cancer, Human Molecular Genetics. (2017) 26, no. 13, 2451–2461, https://doi.org/10.1093/hmg/ddx138, 2-s2.0-85021301214, 28398479.
- 24 Zhang F., Zhang Y.-Y., Sun Y.-S., Ma R.-H., Thakur K., Zhang J.-G., and Wei Z.-J., Asparanin A fromAsparagus officinalisL. induces G0/G1 cell cycle arrest and apoptosis in human endometrial carcinoma Ishikawa cells via mitochondrial and PI3K/AKT signaling pathways, Journal of Agricultural and Food Chemistry. (2019) 68, no. 1, 213–224, https://doi.org/10.1021/acs.jafc.9b07103.
- 25 Sun Y. S., Thakur K., Hu F., Zhang J. G., and Wei Z. J., Icariside II inhibits tumorigenesis via inhibiting AKT/Cyclin E/ CDK 2 pathway and activating mitochondria-dependent pathway, Pharmacological Research. (2020) 152, https://doi.org/10.1016/j.phrs.2019.104616.
- 26 Sun Y. S., Thakur K., Hu F., Cespedes-Acuña C. L., Zhang J. G., and Wei Z. J., Icariside II suppresses cervical cancer cell migration through JNK modulated matrix metalloproteinase-2/9 inhibition in vitro and in vivo, Biomedicine & Pharmacotherapy. (2020) 125, https://doi.org/10.1016/j.biopha.2020.110013.
- 27 Zhang Y. Y., Zhang F., Zhang Y. S., Thakur K., Zhang J. G., Liu Y., Kan H., and Wei Z. J., Mechanism of juglone-induced cell cycle arrest and apoptosis in Ishikawa human endometrial cancer cells, Journal of Agricultural and Food Chemistry. (2019) 67, no. 26, 7378–7389, https://doi.org/10.1021/acs.jafc.9b02759, 2-s2.0-85069264591.
- 28 Huber L. C., Distler O., Tarner I., Gay R. E., Gay S., and Pap T., Synovial fibroblasts: key players in rheumatoid arthritis, Rheumatology (Oxford). (2006) 45, no. 6, 669–675, https://doi.org/10.1093/rheumatology/kel065, 2-s2.0-33745612984, 16567358.
- 29 Miao C. G., Yang Y. Y., He X., Xu T., Huang C., Huang Y., Zhang L., Lv X. W., Jin Y., and Li J., New advances of microRNAs in the pathogenesis of rheumatoid arthritis, with a focus on the crosstalk between DNA methylation and the microRNA machinery, Cellular Signalling. (2013) 25, no. 5, 1118–1125, https://doi.org/10.1016/j.cellsig.2013.01.024, 2-s2.0-84875001588, 23385088.
- 30 Shi D. L., Shi G. R., Xie J., Du X. Z., and Yang H., MicroRNA-27a inhibits cell migration and invasion of fibroblast-like synoviocytes by targeting follistatin-like protein 1 in rheumatoid arthritis, Molecules and Cells. (2016) 39, no. 8, 611–618, https://doi.org/10.14348/molcells.2016.0103, 2-s2.0-85016925020.
- 31 Miao C. G., Yang Y. Y., He X., Huang C., Huang Y., Qin D., du C. L., and Li J., MicroRNA-152 modulates the canonical Wnt pathway activation by targeting DNA methyltransferase 1 in arthritic rat model, Biochimie. (2014) 106, 149–156, https://doi.org/10.1016/j.biochi.2014.08.016, 2-s2.0-84908044011.
- 32 Hong B. K., You S., Yoo S. A., Park D., Hwang D., Cho C. S., and Kim W. U., MicroRNA-143 and -145 modulate the phenotype of synovial fibroblasts in rheumatoid arthritis, Experimental & Molecular Medicine. (2017) 49, no. 8, https://doi.org/10.1038/emm.2017.108, 2-s2.0-85026863628.
- 33 Lian F., Zhao C., Qu J., Lian Y., Cui Y., Shan L., and Yan J., Icariin attenuates titanium particle-induced inhibition of osteogenic differentiation and matrix mineralization via miR-21-5p, Cell Biology International. (2018) 42, no. 8, 931–939, https://doi.org/10.1002/cbin.10957, 2-s2.0-85044427711, 29500883.
- 34 Xu L., Leng H., Shi X., Ji J., Fu J., and Leng H., MiR-155 promotes cell proliferation and inhibits apoptosis by PTEN signaling pathway in the psoriasis, Biomedicine & Pharmacotherapy. (2017) 90, 524–530, https://doi.org/10.1016/j.biopha.2017.03.105, 2-s2.0-85017238938, 28402921.
- 35 Ren L., Zhao Y., Huo X., and Wu X., MiR-155-5p promotes fibroblast cell proliferation and inhibits FOXO signaling pathway in vulvar lichen sclerosis by targeting FOXO3 and CDKN1B, Gene. (2018) 653, 43–50, https://doi.org/10.1016/j.gene.2018.01.049, 2-s2.0-85044357268, 29339071.
- 36 Kurowska-Stolarska M., Alivernini S., Ballantine L. E., Asquith D. L., Millar N. L., Gilchrist D. S., Reilly J., Ierna M., Fraser A. R., Stolarski B., McSharry C., Hueber A. J., Baxter D., Hunter J., Gay S., Liew F. Y., and McInnes I. B., MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis, Proceedings of the National Academy of Sciences of the United States of America. (2011) 108, no. 27, 11193–11198, https://doi.org/10.1073/pnas.1019536108, 2-s2.0-79960595150, 21690378.
- 37 Alivernini S., Kurowska-Stolarska M., Tolusso B., Benvenuto R., Elmesmari A., Canestri S., Petricca L., Mangoni A., Fedele A. L., Di Mario C., Gigante M. R., Gremese E., McInnes I. B., and Ferraccioli G., MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis, Nature Communications. (2016) 7, no. 1, https://doi.org/10.1038/ncomms12970, 2-s2.0-84989308236.
- 38 Cao C., Vasilatos S. N., Bhargava R., Fine J. L., Oesterreich S., Davidson N. E., and Huang Y., Functional interaction of histone deacetylase 5 (HDAC5) and lysine-specific demethylase 1 (LSD1) promotes breast cancer progression, Oncogene. (2017) 36, no. 1, 133–145, https://doi.org/10.1038/onc.2016.186, 2-s2.0-84969785510, 27212032.
- 39
Lv T.,
Yuan D.,
Miao X.,
Lv Y.,
Zhan P.,
Shen X., and
Song Y., Over-expression of LSD1 promotes proliferation, migration and invasion in non-small cell lung cancer, PLoS One. (2012) 7, no. 4, https://doi.org/10.1371/journal.pone.0035065, 2-s2.0-84859480637.
10.1371/journal.pone.0035065 Google Scholar
- 40 Elmesmari A., Fraser A. R., Wood C., Gilchrist D., Vaughan D., Stewart L., McSharry C., McInnes I. B., and Kurowska-Stolarska M., MicroRNA-155 regulates monocyte chemokine and chemokine receptor expression in rheumatoid arthritis, Rheumatology (Oxford). (2016) 55, no. 11, 2056–2065, https://doi.org/10.1093/rheumatology/kew272, 2-s2.0-84997161405, 27411480.