Skip to main content

Advertisement

SpringerLink
Log in

Dysregulation of long non-coding RNAs in Takayasu arteritis: A proof-of-concept study

  • PERSPECTIVES IN RHEUMATOLOGY
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Takayasu arteritis (TAK) is a rare systemic vasculitis primarily affecting the aorta and its major branches. Early diagnosis is critical to prevent severe vascular complications, yet current biomarkers are insufficient. This proof-of-concept study explores the potential of long non-coding RNAs (lncRNAs) in TAK, an area largely unexplored. In this cross-sectional study, 53 TAK patients, 53 healthy controls, and 10 rheumatoid arthritis (RA) patients were enrolled. Clinical evaluations, disease activity assessments, and lncRNA expression levels were analyzed. TAK patients exhibited significant dysregulation in several lncRNAs, including THRIL (19.4, 11.1–48.8 vs. 62.5, 48.6–91.4 arbitrary units [a.u.]; p < 0.0001), HIF1A-AS1 (4.5, 1.8–16.6 vs. 26.5, 19.8–33.7 a.u.; p < 0.0001), MALAT-1 (26.9, 13.8–52.5 vs. 92.1, 58.5–92.1 a.u.; p < 0.0001), and HOTAIR (8.0, 2.5–24.5 vs. 36.0, 30.0–43.8 a.u.; p < 0.0001), compared to healthy controls. Notably, HOTAIR (area under the ROC curve [AUC] = 0.825), HIF1A-AS1 (AUC = 0.820), and THRIL (AUC = 0.781) demonstrated high diagnostic potential with superior specificity (approximately 95%). While lncRNAs showed diagnostic promise, no significant correlations with TAK activity were observed. Comparative analysis with RA patients revealed distinct lncRNA expression patterns. This study unveils significant dysregulation of lncRNAs THRIL, HIF1A-AS1, and HOTAIR in TAK patients, underscoring their potential as biomarkers and opening avenues for further research into the mechanistic roles of these lncRNAs in TAK pathogenesis.

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

Similar content being viewed by others

Data availability

All data are available on request to the corresponding author.

References

  1. Castillo-Martínez D, Amezcua-Guerra LM (2012) Self-reactivity against stress-induced cell molecules: The missing link between Takayasu’s arteritis and tuberculosis? Med Hypotheses 78:485–488. https://doi.org/10.1016/j.mehy.2012.01.012

    Article  CAS  PubMed  Google Scholar 

  2. Joseph G, Goel R, Thomson VS, Joseph E, Danda D (2022) Takayasu arteritis: JACC focus seminar 3/4. J Am Coll Cardiol 81(2):172–186. https://doi.org/10.1016/j.jacc.2022.09.051

  3. Wen D, Feng L, Du X, Dong JZ, Ma CS (2023) Biomarkers in Takayasu arteritis. Int J Cardiol 371:413–417. https://doi.org/10.1016/j.ijcard.2022.08.058

    Article  PubMed  Google Scholar 

  4. Amezcua-Guerra LM, Sánchez-Muñoz F, Pichardo-Ontiveros E, González-Ramírez J, Martínez-Martínez LA, Juárez-Vicuña Y (2022) Interferon-alpha regulates expression of lncRNA MALAT1 and interferon-stimulated genes, as well as chemokine production, in primary Sjögren's syndrome. Clin Exp Rheumatol 40:2275–2282. https://doi.org/10.55563/clinexprheumatol/ggkc9t

  5. Yang K, Tang J, Li H, Zhang H, Ding J, Li Z (2023) Luo J (2023) LncRNAs in Kawasaki disease and Henoch-Schönlein purpura: Mechanisms and clinical applications. Mol Cell Biochem. https://doi.org/10.1007/s11010-023-04832-x

    Article  PubMed  PubMed Central  Google Scholar 

  6. Grayson PC, Ponte C, Suppiah R, Robson JC, Gribbons KB, Judge A, Craven A, Khalid S, Hutchings A, Danda D, Luqmani RA, Watts RA, Merkel PA; DCVAS Study Group (2022) 2022 American College of Rheumatology/EULAR classification criteria for Takayasu arteritis. Ann Rheum Dis 81:1654-1660. https://doi.org/10.1136/ard-2022-223482

  7. Misra R, Danda D, Rajappa SM, Ghosh A, Gupta R, Mahendranath KM, Jeyaseelan L, Lawrence A, Bacon PA, Vasculitis IR, (IRAVAS) group (2013) Development and initial validation of the Indian Takayasu Clinical Activity Score (ITAS2010). Rheumatology 52:1795–1801. https://doi.org/10.1093/rheumatology/ket128

    Article  PubMed  Google Scholar 

  8. Dabague J, Reyes PA (1996) Takayasu arteritis in Mexico: A 38-year clinical perspective through literature review. Int J Cardiol 54(Suppl):S103-109. https://doi.org/10.1016/s0167-5273(96)88779-1

    Article  PubMed  Google Scholar 

  9. Chomczynski P, Sacchi N (2006) The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: Twenty-something years on. Nat Protoc 1:581–585. https://doi.org/10.1038/nprot.2006.83

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Direskeneli H (2017) Clinical assessment in Takayasu’s arteritis: Major challenges and controversies. Clin Exp Rheumatol 35(Suppl 103):189–193

    PubMed  Google Scholar 

  11. Ishihara T, Haraguchi G, Kamiishi T, Tezuka D, Inagaki H, Isobe M (2011) Sensitive assessment of activity of Takayasu’s arteritis by pentraxin3, a new biomarker. J Am Coll Cardiol 57:1712–1713

    Article  PubMed  Google Scholar 

  12. Mahajan N, Dhawan V, Malik S, Jain S (2010) Serum levels of soluble receptor for advanced glycation end products (sRAGE) in Takayasu’s arteritis. Int J Cardiol 145:589–591

    Article  PubMed  Google Scholar 

  13. Li Z, Chao TC, Chang KY, Lin N, Patil VS, Shimizu C, Head SR, Burns JC, Rana TM (2014) The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL. Proc Natl Acad Sci U S A 111:1002–1007. https://doi.org/10.1073/pnas.1313768111

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Castillo-Martínez D, Amezcua-Castillo LM, Granados J, Pineda C, Amezcua-Guerra LM (2020) Is Takayasu arteritis the result of a mycobacterium tuberculosis infection? The use of TNF inhibitors may be the proof-of-concept to demonstrate that this association is epiphenomenal. Clin Rheumatol 39:2003–2009. https://doi.org/10.1007/s10067-020-05045-z

    Article  PubMed  Google Scholar 

  15. Yang J, Gong Z, Dong J, Li H, Wang B, Du K, Zhang C, Chen L (2023) Transcriptomics provides novel insights into the regulatory mechanism of IncRNA HIF1 A-AS1 on vascular smooth muscle cells. Braz J Cardiovasc Surg 38:e20220260. https://doi.org/10.21470/1678-9741-2022-0260

  16. Xu J, Zhang Y, Chu L, Chen W, Du Y, Gu J (2019) Long non-coding RNA HIF1A-AS1 is upregulated in intracranial aneurysms and participates in the regulation of proliferation of vascular smooth muscle cells by upregulating TGF-β1. Exp Ther Med 17:1797–1801. https://doi.org/10.3892/etm.2018.7144

    Article  CAS  PubMed  Google Scholar 

  17. He Q, Tan J, Yu B, Shi W, Liang K (2015) Long noncoding RNA HIF1A-AS1A reduces apoptosis of vascular smooth muscle cells: Implications for the pathogenesis of thoracoabdominal aorta aneurysm. Pharmazie 70:310–315

    CAS  PubMed  Google Scholar 

  18. Zhang X, Li H, Guo X, Hu J, Li B (2020) Long noncoding RNA hypoxia inducible factor-1 alpha-antisense RNA 1 regulates vascular smooth muscle cells to promote the development of thoracic aortic aneurysm by modulating apoptotic protease-activating factor 1 and targeting let-7g. J Surg Res 255:602–611. https://doi.org/10.1016/j.jss.2020.05.063

    Article  CAS  PubMed  Google Scholar 

  19. Amicone L, Marchetti A, Cicchini C (2023) The lncRNA HOTAIR: A pleiotropic regulator of epithelial cell plasticity. J Exp Clin Cancer Res 42:147. https://doi.org/10.1186/s13046-023-02725-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wei Z, Chen L, Meng L, Han W, Huang L, Xu A (2020) LncRNA HOTAIR promotes the growth and metastasis of gastric cancer by sponging miR-1277-5p and upregulating COL5A1. Gastric Cancer 23:1018–1032. https://doi.org/10.1007/s10120-020-01091-3

    Article  CAS  PubMed  Google Scholar 

  21. Jia R, Li T, Wang N (2021) Long noncoding RNA HOTAIR functions as ceRNA to regulate MMP2 in paraquat induced lung epithelial-mesenchymal transition. Toxicology 461:152891. https://doi.org/10.1016/j.tox.2021.152891

    Article  CAS  PubMed  Google Scholar 

  22. Qiu H, Liu M, Shi X, Ma M, Zhang J, Liu H (2022) LncRNA HOTAIR inhibits the progression of fibroblast-like synoviocytes by sponging miRNA-106b-5p in rheumatoid arthritis. Autoimmunity 55:567–576. https://doi.org/10.1080/08916934.2022.2126460

    Article  CAS  PubMed  Google Scholar 

  23. Song J, Kim D, Han J, Kim Y, Lee M, Jin EJ (2015) PBMC and exosome-derived Hotair is a critical regulator and potent marker for rheumatoid arthritis. Clin Exp Med 15:121–126. https://doi.org/10.1007/s10238-013-0271-4

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Escuela Nacional de Ciencias Biológicas (ENCB), Instituto Politécnico Nacional, Mexico City, Mexico

    Fernanda Espinosa-Bautista

  2. Immunology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección XVI, 14080, Tlalpan, Mexico City, Mexico

    Fernanda Espinosa-Bautista, Malinalli Brianza-Padilla & Luis M. Amezcua-Guerra

  3. Laboratorio Nacional de Vacunología y Virus Tropicales, Escuela Nacional de Ciencias Biológicas (ENCB), Instituto Politécnico Nacional, Mexico City, Mexico

    Ma. Isabel Salazar-Sánchez

  4. Departamento de Zoología, Escuela Nacional de Ciencias Biológicas (ENCB), Instituto Politécnico Nacional, Mexico City, Mexico

    Gloria León-Ávila

  5. Laboratorio de Investigación de Obesidad y Asma, Hospital Infantil de México Federico Gómez, Mexico City, Mexico

    Adrián Hernández-Díazcouder

  6. Laboratorio de Inmunoquímica I, Escuela Nacional de Ciencias Biológicas (ENCB), Instituto Politécnico Nacional, Mexico City, Mexico

    María Lilia Domínguez-López

  7. Health Care Department, Universidad Autónoma Metropolitana–Xochimilco, Mexico City, Mexico

    Luis M. Amezcua-Guerra

  8. Directorate, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, Mexico

    Carlos Pineda

Authors
  1. Fernanda Espinosa-Bautista
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ma. Isabel Salazar-Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Malinalli Brianza-Padilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gloria León-Ávila
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Adrián Hernández-Díazcouder
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. María Lilia Domínguez-López
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Luis M. Amezcua-Guerra
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Carlos Pineda
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study’s conception and design. Clinical assessments were performed by Fernanda Espinosa-Bautista. Laboratory assays were performed by Fernanda Espinosa-Bautista, Malinalli Brianza-Padilla, and Adrián Hernández-Díazcouder. Material preparation and data collection were performed by Fernanda Espinosa-Bautista and Luis M Amezcua-Guerra. Statistical analysis was performed by Fernanda Espinosa-Bautista and Luis M Amezcua-Guerra. The first draft of the manuscript was written by Fernanda Espinosa-Bautista and Luis M Amezcua-Guerra and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Luis M. Amezcua-Guerra.

Ethics declarations

Disclosures

None.

Informed consent

Participants authorized the use of medical data for research purposes.

Ethical approval

This study was approved by the institutional review board (Comité de Ética en Investigación del Instituto Nacional de Cardiología Ignacio Chávez) with the protocol number 23–1363.

Human rights

All procedures followed the 2013 Declaration of Helsinki and local regulations.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Espinosa-Bautista, F., Salazar-Sánchez, M.I., Brianza-Padilla, M. et al. Dysregulation of long non-coding RNAs in Takayasu arteritis: A proof-of-concept study. Clin Rheumatol 43, 1253–1259 (2024). https://doi.org/10.1007/s10067-024-06880-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-024-06880-0

Keywords

Search

Navigation