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CircASH2L facilitates tumor-like biologic behaviours and inflammation of fibroblast-like synoviocytes via miR-129-5p/HIPK2 axis in rheumatoid arthritis

Li, Xia, Qu, Meiting, Zhang, Jie, Chen, Kuanyin, Ma, Xianghui·2021·Journal of Orthopaedic Surgery and Research
DOI 10.1186/s13018-021-02432-3PMC PMC8106127
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Abstract

Background: Previous study showed that circular RNA Absent-Small-Homeotic-2--Like protein (circASH2L) was higher in rheumatoid arthritis (RA) patients. However, the roles and mechanisms of circASH2L in RA progression remain unclear. Methods: Levels analysis was conducted using western blot and qRT-PCR. The proliferation, apoptosis, cell cycle progression, migration, invasiveness, and inflammation of RA fibroblast-like synoviocytes (RA-FLSs) were determined via MTT, flow cytometry, western blot, transwell, and ELISA assays. Results: CircASH2L knockdown in RA-FLSs suppressed cell proliferative, migratory, and invasive capacities, triggered cell cycle arrest, promoted apoptosis, and inhibited inflammation. Mechanistically, circASH2L targeted miR-129-5p, and repression of miR-129-5p abolished the functions of circASH2L silencing on the growth, motility, and inflammation of RA-FLSs. Besides, miR-129-5p was found to directly target HIPK2, and suppressed the tumor-like biologic behaviors and inflammation of RA-FLSs via regulating HIPK2. Importantly, we proved that circASH2L could modulate HIPK2 expression via miR-129-5p. Conclusion: CircASH2L promoted RA-FLS growth, motility, and inflammation through miR-129-5p/HIPK2 axis.

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Fig. 1 CircASH2L expression in RA. a Schematic illustration demonstrates the formation of circASH2L via the circularization of exons 11 and 12 in ASH2L. b, c Detection of circASH2L expression in synovial tissues with RA and non-RA, as well as in RA-FLSs and N-FLSs with qRT-PCR. d Detection of circASH2L and linear ASH2L mRNA expression in RA-FLSs after RNase R treatment using qRT-PCR analysis. *P<0.05
Fig. 1 CircASH2L expression in RA. a Schematic illustration demonstrates the formation of circASH2L via the circularization of exons 11 and 12 in ASH2L. b, c Detection of circASH2L expression in synovial tissues with RA and non-RA, as well as in RA-FLSs and N-FLSs with qRT-PCR. d Detection of circASH2L and linear ASH2L mRNA expression in RA-FLSs after RNase R treatment using qRT-PCR analysis. *P<0.05CC BY · PubMed Central
Fig. 2 Effects of circASH2L on the tumor-like biologic behaviors of RA-FLSs. a-i si-circASH2L or si-NC was transfected into RA-FLSs, respectively. a Measurement of circASH2L expression in RA-FLSs with qRT-PCR. b, c Cell proliferation analysis with MTT assay and Edu assay. d Flow cytometry for cell apoptosis. e Detection of apoptosis-related protein using western blot. f Flow cytometry of cell cycle analysis. g, h Cell migration and invasion analysis with transwell assay. i Detection of inflammatory cytokines expression using ELISA. *P<0.05
Fig. 2 Effects of circASH2L on the tumor-like biologic behaviors of RA-FLSs. a-i si-circASH2L or si-NC was transfected into RA-FLSs, respectively. a Measurement of circASH2L expression in RA-FLSs with qRT-PCR. b, c Cell proliferation analysis with MTT assay and Edu assay. d Flow cytometry for cell apoptosis. e Detection of apoptosis-related protein using western blot. f Flow cytometry of cell cycle analysis. g, h Cell migration and invasion analysis with transwell assay. i Detection of inflammatory cytokines expression using ELISA. *P<0.05CC BY · PubMed Central
Fig. 3 CircASH2L directly bind to miR-129-5p in RA-FLSs. a Binding sites between miR-129-5p and circASH2L. b Interaction analysis between miR-129-5p and circASH2L using the dual-luciferase reporter assay. c, d MiR-129-5p expression in synovial tissues with RA and non-RA, as well as in RA-FLSs and N-FLSs was examined by qRT-PCR. e qRT-PCR analysis of miR-129-5p expression in circASH2L-decreased RA-FLSs. *P<0.05
Fig. 3 CircASH2L directly bind to miR-129-5p in RA-FLSs. a Binding sites between miR-129-5p and circASH2L. b Interaction analysis between miR-129-5p and circASH2L using the dual-luciferase reporter assay. c, d MiR-129-5p expression in synovial tissues with RA and non-RA, as well as in RA-FLSs and N-FLSs was examined by qRT-PCR. e qRT-PCR analysis of miR-129-5p expression in circASH2L-decreased RA-FLSs. *P<0.05CC BY · PubMed Central
Fig. 4 Knockdown of circASH2L suppresses the tumor-like biologic behaviors of RA-FLSs through miR-129-5p. a-i RA-FLSs were co-transfected with si-circASH2L and/or anti-miR-129-5p. a qRT-PCR analysis of miR-129-5p expression in RA-FLSs. b, c Cell proliferation analysis using MTT assay and Edu assay. d Flow cytometry of cell apoptosis analysis. e Detection of apoptosis-related protein expression using western blot. f Flow cytometry of cell cycle analysis. g, h The migratory and invasive activities analysis of cells using transwell assay. i) The measurement of inflammatory cytokines levels using ELISA. *P<0.05
Fig. 4 Knockdown of circASH2L suppresses the tumor-like biologic behaviors of RA-FLSs through miR-129-5p. a-i RA-FLSs were co-transfected with si-circASH2L and/or anti-miR-129-5p. a qRT-PCR analysis of miR-129-5p expression in RA-FLSs. b, c Cell proliferation analysis using MTT assay and Edu assay. d Flow cytometry of cell apoptosis analysis. e Detection of apoptosis-related protein expression using western blot. f Flow cytometry of cell cycle analysis. g, h The migratory and invasive activities analysis of cells using transwell assay. i) The measurement of inflammatory cytokines levels using ELISA. *P<0.05CC BY · PubMed Central
Fig. 5 CircASH2L indirectly regulates HIPK2 via miR-129-5p in RA-FLSs. a Binding sites of miR-129-5p on HIPK2 3′UTR. b Interaction analysis between miR-129-5p and HIPK2 using the dual-luciferase reporter assay. c-f HIPK2 expression level in synovial tissues with RA and non-RA, as well as in RA-FLSs and N-FLSs was determined. g MiR-129-5p expression analysis using qRT-PCR in RA-FLSs transfected with miR-NC or miR-129-5p. h, i HIPK2 expression analysis in miR-129-5p-increased RA-FLSs with qRT-PCR and western blot. j, k RA-FLSs were co-transfected with si-circASH2L and/or anti-miR-129-5p and HIPK2 level was examined using qRT-PCR and western blot. *P<0.05
Fig. 5 CircASH2L indirectly regulates HIPK2 via miR-129-5p in RA-FLSs. a Binding sites of miR-129-5p on HIPK2 3′UTR. b Interaction analysis between miR-129-5p and HIPK2 using the dual-luciferase reporter assay. c-f HIPK2 expression level in synovial tissues with RA and non-RA, as well as in RA-FLSs and N-FLSs was determined. g MiR-129-5p expression analysis using qRT-PCR in RA-FLSs transfected with miR-NC or miR-129-5p. h, i HIPK2 expression analysis in miR-129-5p-increased RA-FLSs with qRT-PCR and western blot. j, k RA-FLSs were co-transfected with si-circASH2L and/or anti-miR-129-5p and HIPK2 level was examined using qRT-PCR and western blot. *P<0.05CC BY · PubMed Central
Fig. 6 MiR-129-5p impairs RA-FLS tumor-like biologic behaviors through HIPK2. The miR-129-5p and/or HIPK2 were co-transfected into RA-FLSs. After transfection, a western blot analysis of HIPK2 expression using western blot; b, c MTT assay of cell proliferation and Edu assay; d flow cytometry of cell apoptosis detection; e western blot analysis of apoptosis-related protein expression in cells; f flow cytometry for cell cycle analysis; g, h cell migratory and invasive abilities detection using transwell assay; i the measurement of inflammatory cytokines levels using ELISA. *P<0.05
Fig. 6 MiR-129-5p impairs RA-FLS tumor-like biologic behaviors through HIPK2. The miR-129-5p and/or HIPK2 were co-transfected into RA-FLSs. After transfection, a western blot analysis of HIPK2 expression using western blot; b, c MTT assay of cell proliferation and Edu assay; d flow cytometry of cell apoptosis detection; e western blot analysis of apoptosis-related protein expression in cells; f flow cytometry for cell cycle analysis; g, h cell migratory and invasive abilities detection using transwell assay; i the measurement of inflammatory cytokines levels using ELISA. *P<0.05CC BY · PubMed Central

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Research works printed but not linked: 29

  1. McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet (London, England). 2017;389(10086):2328–37. · DOI
  2. Covic T, Cumming SR, Pallant JF, Manolios N, Emery P, Conaghan PG, et al. Depression and anxiety in patients with rheumatoid arthritis: prevalence rates based on a comparison of the Depression, Anxiety and Stress Scale (DASS) and the hospital, Anxiety and Depression Scale (HADS). BMC psychiatry. 2012;12(1):6. https://doi.org/10.1186/1471-244X-12-6. · DOI
  3. Croia C, Bursi R, Sutera D, Petrelli F, Alunno A, Puxeddu I. One year in review 2019: pathogenesis of rheumatoid arthritis. Clinical and experimental rheumatology. 2019;37(3):347–57.
  4. Neumann E, Lefèvre S, Zimmermann B, Gay S, Müller-Ladner U. Rheumatoid arthritis progression mediated by activated synovial fibroblasts. Trends in molecular medicine. 2010;16(10):458–68. https://doi.org/10.1016/j.molmed.2010.07.004. · DOI
  5. Bottini N, Firestein GS. Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors. Nature reviews Rheumatology. 2013;9(1):24–33. https://doi.org/10.1038/nrrheum.2012.190. · DOI
  6. Lefevre S, Meier FM, Neumann E, Muller-Ladner U. Role of synovial fibroblasts in rheumatoid arthritis. Current pharmaceutical design. 2015;21(2):130–41. https://doi.org/10.2174/1381612820666140825122036. · DOI
  7. Rybak-Wolf A, Stottmeister C, Glažar P, Jens M, Pino N, Giusti S, et al. Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. Molecular cell. 2015;58(5):870–85. https://doi.org/10.1016/j.molcel.2015.03.027. · DOI · Paper page
  8. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495(7441):333–8. https://doi.org/10.1038/nature11928. · DOI · Paper page
  9. Zhou R, Wu Y, Wang W, Su W, Liu Y, Wang Y, et al. Circular RNAs (circRNAs) in cancer. Cancer letters. 2018;425:134–42. https://doi.org/10.1016/j.canlet.2018.03.035. · DOI
  10. Yu CY, Kuo HC. The emerging roles and functions of circular RNAs and their generation. Journal of biomedical science. 2019;26(1):29. https://doi.org/10.1186/s12929-019-0523-z. · DOI
  11. Marques-Rocha JL, Samblas M, Milagro FI, Bressan J, Martínez JA, Marti A. Noncoding RNAs, cytokines, and inflammation-related diseases. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2015;29(9):3595–611. https://doi.org/10.1096/fj.14-260323. · DOI
  12. Vo JN, Cieslik M, Zhang Y, Shukla S, Xiao L, Zhang Y, et al. The landscape of circular RNA in cancer. Cell. 2019;176(4):869–81 e813. · DOI
  13. Altesha MA, Ni T, Khan A, Liu K, Zheng X. Circular RNA in cardiovascular disease. Journal of cellular physiology. 2019;234(5):5588–600. https://doi.org/10.1002/jcp.27384. · DOI
  14. Chen X, Yang T, Wang W, Xi W, Zhang T, Li Q, et al. Circular RNAs in immune responses and immune diseases. Theranostics. 2019;9(2):588–607. https://doi.org/10.7150/thno.29678. · DOI
  15. Li B, Li N, Zhang L, Li K, Xie Y, Xue M, et al. Hsa_circ_0001859 regulates ATF2 expression by functioning as an MiR-204/211 sponge in human rheumatoid arthritis. J Immunology Res. 2018;2018:9412387.
  16. Tang X, Wang J, Xia X, Tian J, Rui K, Xu H, et al. Elevated expression of ciRS-7 in peripheral blood mononuclear cells from rheumatoid arthritis patients. Diagnostic pathology. 2019;14(1):11. https://doi.org/10.1186/s13000-019-0783-7. · DOI
  17. Zheng F, Yu X, Huang J, Dai Y. Circular RNA expression profiles of peripheral blood mononuclear cells in rheumatoid arthritis patients, based on microarray chip technology. Molecular medicine reports. 2017;16(6):8029–36. https://doi.org/10.3892/mmr.2017.7638. · DOI
  18. Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunological reviews. 2010;233(1):233–55. https://doi.org/10.1111/j.0105-2896.2009.00859.x. · DOI
  19. Jeck WR, Sharpless NE. Detecting and characterizing circular RNAs. Nature biotechnology. 2014;32(5):453–61. https://doi.org/10.1038/nbt.2890. · DOI
  20. Jin Y, Shenoy AK, Doernberg S, Chen H, Luo H, Shen H, et al. FBXO11 promotes ubiquitination of the Snail family of transcription factors in cancer progression and epidermal development. Cancer letters. 2015;362(1):70–82. https://doi.org/10.1016/j.canlet.2015.03.037. · DOI
  21. Luo Q, Liu J, Fu B, Zhang L, Guo Y, Huang Z, et al. Circular RNAs Hsa_circ_0002715 and Hsa_circ_0035197 in peripheral blood are novel potential biomarkers for new-onset rheumatoid arthritis. Disease markers. 2019;2019:2073139.
  22. Luo Q, Zhang L, Li X, Fu B, Deng Z, Qing C, et al. Identification of circular RNAs hsa_circ_0044235 in peripheral blood as novel biomarkers for rheumatoid arthritis. Clinical and experimental immunology. 2018;194(1):118–24. https://doi.org/10.1111/cei.13181. · DOI
  23. Ouyang Q, Wu J, Jiang Z, Zhao J, Wang R, Lou A, et al. Microarray expression profile of circular RNAs in peripheral blood mononuclear cells from rheumatoid arthritis patients. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2017;42(2):651–9. https://doi.org/10.1159/000477883. · DOI
  24. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495(7441):384–8. https://doi.org/10.1038/nature11993. · DOI · Paper page
  25. Chien Y, Tsai PH, Lai YH, Lu KH, Liu CY, Lin HF, et al. CircularRNA as novel biomarkers in liver diseases. Journal of the Chinese Medical Association : JCMA. 2020;83(1):15–7. https://doi.org/10.1097/JCMA.0000000000000230. · DOI
  26. Zhang Y, Yan N, Wang X, Chang Y, Wang Y. MiR-129-5p regulates cell proliferation and apoptosis via IGF-1R/Src/ERK/Egr-1 pathway in RA-fibroblast-like synoviocytes. Bioscience Rep. 2019;39:12.
  27. Saul VV, Schmitz ML. Posttranslational modifications regulate HIPK2, a driver of proliferative diseases. J Mol Med (Berlin, Germany). 2013;91(9):1051–8. · DOI
  28. Blaquiere JA, Verheyen EM. Homeodomain-interacting protein kinases: diverse and complex roles in development and disease. Curr Topics Dev Biol. 2017;123:73–103. https://doi.org/10.1016/bs.ctdb.2016.10.002. · DOI
  29. Li Y, Lai-Han Leung E, Pan H, Yao X, Huang Q, Wu M, et al. Identification of potential genetic causal variants for rheumatoid arthritis by whole-exome sequencing. Oncotarget. 2017;8(67):111119–29. https://doi.org/10.18632/oncotarget.22630. · DOI

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Metadata

Authors
Li, X., Qu, M., Zhang, J., Chen, K., & Ma, X.
Venue
Journal of Orthopaedic Surgery and Research
Publisher
Springer Science and Business Media LLC
Published
2021-05-08
Volume
16
Issue
1
ISSN
1749-799X
DOI
10.1186/s13018-021-02432-3
PMC
PMC8106127
Cited by
18
References
1
Language
en
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Li, X., Qu, M., Zhang, J., Chen, K., & Ma, X. (2021). CircASH2L facilitates tumor-like biologic behaviours and inflammation of fibroblast-like synoviocytes via miR-129-5p/HIPK2 axis in rheumatoid arthritis. Journal of Orthopaedic Surgery and Research. https://doi.org/10.1186/s13018-021-02432-3