Skip to main content

Advertisement

SpringerLink
Log in

LncRNA ZFAS1 promotes cell migration and invasion of fibroblast-like synoviocytes by suppression of miR-27a in rheumatoid arthritis

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Rheumatoid arthritis (RA) is a systemic and chronic inflammatory disease. Synoviocyte migration and invasion were found to be essential to the pathology of RA. Upregulation of long noncoding RNA ZFAS1 has been observed in cancers and promotes cell migration and invasion. To date, the functions and mechanisms of ZFAS1 in RA have not been revealed. In this study, we analyzed expression pattern of ZFAS1 in RA patients and found that ZFAS1 expression was increased in synovial tissue and fibroblast-like synoviocytes (FLS) from RA patients (RA-FLS) compared with that in healthy donors. Functional assays showed that silence of ZFAS1 suppressed RA-FLS migration and invasion, while overexpression of ZFAS1 showed the opposite effect. Further investigation demonstrated that ZFAS1 directly interacted with miR-27a and decreased miR-27a expression. ZFAS1 promotes RA-FLS migration and invasion in an miR-27a-dependent manner. Taken together, the present study provides the first evidence that ZFAS1 promotes cell migration and invasion through miR-27a in RA-FLS, suggesting that ZFAS1 may be an effective therapeutic target for RA patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Araki Y, Mimura T. The mechanisms underlying chronic inflammation in rheumatoid arthritis from the perspective of the epigenetic landscape. J Immunol Res. 2016;2016:6290682. doi:10.1155/2016/6290682.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Liu Y, Pan YF, Xue YQ, Fang LK, Guo XH, Guo X, et al. uPAR promotes tumor-like biologic behaviors of fibroblast-like synoviocytes through PI3K/Akt signaling pathway in patients with rheumatoid arthritis. Cell Mol Immunol. 2017. doi:10.1038/cmi.2016.60.

    PubMed Central  Google Scholar 

  3. Shang CH, Zhang QQ, Zhou JH. Oridonin inhibits cell proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes. Inflammation. 2016;39(2):873–80. doi:10.1007/s10753-016-0318-2.

    Article  CAS  PubMed  Google Scholar 

  4. Ospelt C, Neidhart M, Gay RE, Gay S. Synovial activation in rheumatoid arthritis. Front Biosci. 2004;9:2323–34.

    Article  CAS  PubMed  Google Scholar 

  5. Zeng S, Wang K, Huang M, Qiu Q, Xiao Y, Shi M, et al. Halofuginone inhibits TNF-alpha-induced the migration and proliferation of fibroblast-like synoviocytes from rheumatoid arthritis patients. Int Immunopharmacol. 2017;43:187–94. doi:10.1016/j.intimp.2016.12.016.

    Article  CAS  PubMed  Google Scholar 

  6. Nakamachi Y, Kawano S, Takenokuchi M, Nishimura K, Sakai Y, Chin T, et al. MicroRNA-124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Rheum. 2009;60(5):1294–304. doi:10.1002/art.24475.

    Article  PubMed  Google Scholar 

  7. Chen Y, Xian PF, Yang L, Wang SX. MicroRNA-21 promotes proliferation of fibroblast-like synoviocytes through mediation of NF-kappaB nuclear translocation in a rat model of collagen-induced rheumatoid arthritis. Biomed Res Int. 2016;2016:9279078. doi:10.1155/2016/9279078.

    PubMed  PubMed Central  Google Scholar 

  8. Lin J, Huo R, Xiao L, Zhu X, Xie J, Sun S, et al. A novel p53/microRNA-22/Cyr61 axis in synovial cells regulates inflammation in rheumatoid arthritis. Arthritis Rheumatol. 2014;66(1):49–59. doi:10.1002/art.38142.

    Article  CAS  PubMed  Google Scholar 

  9. Wang J, Ye C, Xiong H, Shen Y, Lu Y, Zhou J, et al. Dysregulation of long non-coding RNA in breast cancer: an overview of mechanism and clinical implication. Oncotarget. 2017;8(3):5508–22. doi:10.18632/oncotarget.12537.

    PubMed  Google Scholar 

  10. Su Y, Wu H, Pavlosky A, Zou LL, Deng X, Zhang ZX, et al. Regulatory non-coding RNA: new instruments in the orchestration of cell death. Cell Death Dis. 2016;7(8):e2333. doi:10.1038/cddis.2016.210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Guo X, Hua Y. CCAT1: an oncogenic long noncoding RNA in human cancers. J Cancer Res Clin Oncol. 2016. doi:10.1007/s00432-016-2268-3.

    Google Scholar 

  12. Busch A, Eken SM, Maegdefessel L. Prospective and therapeutic screening value of non-coding RNA as biomarkers in cardiovascular disease. Ann Transl Med. 2016;4(12):236. doi:10.21037/atm.2016.06.06.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lu MC, Yu HC, Yu CL, Huang HB, Koo M, Tung CH, et al. Increased expression of long noncoding RNAs LOC100652951 and LOC100506036 in T cells from patients with rheumatoid arthritis facilitates the inflammatory responses. Immunol Res. 2016;64(2):576–83. doi:10.1007/s12026-015-8756-8.

    Article  CAS  PubMed  Google Scholar 

  14. Li T, Xie J, Shen C, Cheng D, Shi Y, Wu Z, et al. Amplification of long noncoding RNA ZFAS1 promotes metastasis in hepatocellular carcinoma. Cancer Res. 2015;75(15):3181–91. doi:10.1158/0008-5472.CAN-14-3721.

    Article  CAS  PubMed  Google Scholar 

  15. Nie F, Yu X, Huang M, Wang Y, Xie M, Ma H, et al. Long noncoding RNA ZFAS1 promotes gastric cancer cells proliferation by epigenetically repressing KLF2 and NKD2 expression. Oncotarget. 2016. doi:10.18632/oncotarget.9611.

    Google Scholar 

  16. Fang C, Zan J, Yue B, Liu C, He C, Yan D. Long Noncoding RNA ZFAS1 promotes the progression of colonic cancer by modulating ZEB1 expression. J Gastroenterol Hepatol. 2016. doi:10.1111/jgh.13646.

    Google Scholar 

  17. Zhang Y, Xu YZ, Sun N, Liu JH, Chen FF, Guan XL, et al. Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Res Ther. 2016;18(1):227. doi:10.1186/s13075-016-1129-4.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yang F, Zhang L, Huo XS, Yuan JH, Xu D, Yuan SX, et al. Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology. 2011;54(5):1679–89. doi:10.1002/hep.24563.

    Article  CAS  PubMed  Google Scholar 

  19. Hu X, Feng Y, Zhang D, Zhao SD, Hu Z, Greshock J, et al. A functional genomic approach identifies FAL1 as an oncogenic long noncoding RNA that associates with BMI1 and represses p21 expression in cancer. Cancer Cell. 2014;26(3):344–57. doi:10.1016/j.ccr.2014.07.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bayoumi AS, Sayed A, Broskova Z, Teoh JP, Wilson J, Su H, et al. Crosstalk between long noncoding RNAs and microRNAs in health and disease. Int J Mol Sci. 2016;17(3):356. doi:10.3390/ijms17030356.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Liu Q, Zhang X, Dai L, Hu X, Zhu J, Li L, et al. Long noncoding RNA related to cartilage injury promotes chondrocyte extracellular matrix degradation in osteoarthritis. Arthritis Rheumatol. 2014;66(4):969–78. doi:10.1002/art.38309.

    Article  CAS  PubMed  Google Scholar 

  22. Shi J, Dong B, Cao J, Mao Y, Guan W, Peng Y, et al. Long non-coding RNA in glioma: signaling pathways. Oncotarget. 2017. doi:10.18632/oncotarget.15175.

    Google Scholar 

  23. Yuan JH, Yang F, Wang F, Ma JZ, Guo YJ, Tao QF, et al. A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014;25(5):666–81. doi:10.1016/j.ccr.2014.03.010.

    Article  CAS  PubMed  Google Scholar 

  24. Wu Q, Han L, Yan W, Ji X, Han R, Yang J, et al. miR-489 inhibits silica-induced pulmonary fibrosis by targeting MyD88 and Smad3 and is negatively regulated by lncRNA CHRF. Sci Rep. 2016;6:30921. doi:10.1038/srep30921.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hu L, Ye H, Huang G, Luo F, Liu Y, Liu Y, et al. Long noncoding RNA GAS5 suppresses the migration and invasion of hepatocellular carcinoma cells via miR-21. Tumour Biol. 2016;37(2):2691–702. doi:10.1007/s13277-015-4111-x.

    Article  CAS  PubMed  Google Scholar 

  26. Shi DL, Shi GR, Xie J, Du XZ, Yang H. MicroRNA-27a inhibits cell migration and invasion of fibroblast-like synoviocytes by targeting follistatin-like protein 1 in rheumatoid arthritis. Mol Cells. 2016;39(8):611–8. doi:10.14348/molcells.2016.0103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Xia B, Hou Y, Chen H, Yang S, Liu T, Lin M, et al. Long non-coding RNA ZFAS1 interacts with miR-150-5p to regulate Sp1 expression and ovarian cancer cell malignancy. Oncotarget. 2017;8(12):19534–46. doi:10.18632/oncotarget.14663.

    PubMed  PubMed Central  Google Scholar 

  28. Wu T, Wu D, Wu Q, Zou B, Huang X, Cheng X, et al. Knockdown of long non-coding RNA-ZFAS1 protects cardiomyocytes against acute myocardial infarction via anti-apoptosis by regulating miR-150/CRP. J Cell Biochem. 2017. doi:10.1002/jcb.25979.

    PubMed Central  Google Scholar 

  29. Hansji H, Leung EY, Baguley BC, Finlay GJ, Cameron-Smith D, Figueiredo VC, et al. ZFAS1: a long noncoding RNA associated with ribosomes in breast cancer cells. Biol Direct. 2016;11(1):62. doi:10.1186/s13062-016-0165-y.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Immunology Department, Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Jiangyang District, Luzhou, Sichuan, China

    Yang Ye & Xiaomei Gao

  2. Immunology Department, West China Hospital of Sichuan University, Chengdu, China

    Nanping Yang

Authors
  1. Yang Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaomei Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nanping Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yang Ye.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 69 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ye, Y., Gao, X. & Yang, N. LncRNA ZFAS1 promotes cell migration and invasion of fibroblast-like synoviocytes by suppression of miR-27a in rheumatoid arthritis. Human Cell 31, 14–21 (2018). https://doi.org/10.1007/s13577-017-0179-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-017-0179-5

Keywords

Search

Navigation