The Immunomodulatory Role of Glucokinase 1 (GCK1) lncRNA in Patients With COVID-19
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Abstract
Individuals infected with Coronavirus Disease 2019 (COVID-19) may exhibit a wide range of clinical symptoms, from asymptomatic cases to severe complications. This variation is likely associated with differences in immune response intensity, where specific long noncoding RNAs (lncRNAs) are known to regulate the interferon (IFN) signaling pathway. The present study aimed to comparatively investigate the relationship between Glucokinase 1 (GCK1) lncRNA expression and immune system activity in individuals with COVID-19. A total of 100 participants were included in the study. The expression of the GCK1 lncRNA gene was quantified using quantitative real-time polymerase chain reaction (qPCR), and the concentrations of IL-12, IFN-α, IFN-γ, and tumor necrosis factor-alpha (TNF-α) in cell culture supernatants were measured via Enzyme-Linked Immunosorbent Assay (ELISA). The findings revealed a significant upregulation of lncRNA-GCK1 expression in COVID-19 patients compared with the control group. Additionally, the levels of IL-12, IFN-α, TNF-α, and IFN-γ were considerably higher in patients, suggesting a potential association between increased lncRNA-GCK1 expression and an intensified inflammatory response. Collectively, the findings highlight lncRNA-GCK1 as a potential key regulator of immune activation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and a promising biomarker candidate for monitoring disease dynamics and treatment outcomes.
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24. Enguita FJ, Leitão AL, McDonald JT, Zaksas V, Das S, Galeano D, et al. The interplay between lncRNAs, RNA-binding proteins and viral genome during SARS-CoV-2 infection reveals strong connections with regulatory events involved in RNA metabolism and immune response. Theranostics 2022;12:3946-3962.
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28. Huang K, Wang C, Vagts C, Raguveer V, Finn PW, Perkins DL. Long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 are differentially expressed in severe COVID-19 patients: An integrated single cell analysis. PLoS One 2022;17:e0261242.
29. Martinez-Castillo M, M Elsayed A, López-Berestein G, Amero P, Rodríguez-Aguayo C. An Overview of the Immune Modulatory Properties of Long Non-Coding RNAs and Their Potential Use as Therapeutic Targets in Cancer. Noncoding RNA 2023;9:70.
2. Sharma A, Tiwari S, Deb MK, Marty JL. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): a global pandemic and treatment strategies. Int J Antimicrob Agents 2020;56:106054.
3. Dumache R, Enache A, Macasoi I, Dehelean CA, Dumitrascu V, Mihailescu A, et al. SARS-CoV-2: An Overview of the Genetic Profile and Vaccine Effectiveness of the Five Variants of Concern. Pathogens 2022;11:516.
4. Yang Y, Shen C, Li J, Yuan J, Wei J, Huang F, et al. Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19. J Allergy Clin Immunol 2020;146:119-127.e4.
5. Schultze JL, Aschenbrenner AC. COVID-19 and the human innate immune system. Cell 2021;184:1671-92.
6. Amini A, Khadivar P, Ahmadnia A, Alipour M, Majeed M, Jamialahmadi T, et al. Role of Curcumin in Regulating Long Noncoding RNA Expression in Cancer. Adv Exp Med Biol 2021;1308:13-23.
7. Jiang M, Zhang S, Yang Z, Lin H, Zhu J, Liu L, et al. Self-Recognition of an Inducible Host lncRNA by RIG-I Feedback Restricts Innate Immune Response. Cell 2018;173:906-19.e13.
8. Min J, Liu W, Li J. Emerging Role of Interferon-Induced Noncoding RNA in Innate Antiviral Immunity. Viruses 2022;14:2607.
9. Guo C, Ludvik AE, Arlotto ME, Hayes MG, Armstrong LL, Scholtens DM, et al. Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1. Nat Commun 2015;6:6069.
10. Claeyssen E, Rivoal J. Isozymes of plant hexokinase: occurrence, properties and functions. Phytochemistry 2007;68:709-31.
11. Abu Aqel Y, Alnesf A, Aigha II, Islam Z, Kolatkar PR, Teo A, et al. Glucokinase (GCK) in diabetes: from molecular mechanisms to disease pathogenesis. Cell Mol Biol Lett 2024;29:120.
12. Turgeon CT, Sanders KA, Granger D, Nett SL, Hilgart H, Matern D, et al. Detection of SARS-CoV-2 IgG antibodies in dried blood spots. Diagn Microbiol Infect Dis 2021;101:115425.
13. Doleshal M, Magotra AA, Choudhury B, Cannon BD, Labourier E, Szafranska AE. Evaluation and validation of total RNA extraction methods for microRNA expression analyses in formalin-fixed, paraffin-embedded tissues. J Mol Diagn 2008;10:203-11.
14. He R, Du Y, Gan L, Mohsin MA, He BX. Development of a SYBR Green-based real-time quantitative polymerase chain reaction assay to detect enzootic nasal tumor virus in goats. Can J Vet Res 2021;85:145-50.
15. Lee JS, Song CH, Kim CH, Kong SJ, Shon MH, et al. Profiles of IFN-gamma and its regulatory cytokines (IL-12, IL-18 and IL-10) in peripheral blood mononuclear cells from patients with multidrug-resistant tuberculosis. Clin Exp Immunol 2002;128:516-24.
16. Baj J, Karakuła-Juchnowicz H, Teresiński G, Buszewicz G, Ciesielka M, Sitarz R, et al. COVID-19: Specific and Non-Specific Clinical Manifestations and Symptoms: The Current State of Knowledge. J Clin Med 2020;9:1753.
17. Hirano T. IL-6 in inflammation, autoimmunity and cancer. Int Immunol 2021;33:127-48.
18. Sapna F, Deepa F, Sakshi F, Sonam F, Kiran F, Perkash RS, et al. Unveiling the Mysteries of Long COVID Syndrome: Exploring the Distinct Tissue and Organ Pathologies Linked to Prolonged COVID-19 Symptoms. Cureus 2023;15:e44588.
19. Kim YM, Shin EC. Type I and III interferon responses in SARS-CoV-2 infection. Exp Mol Med 2021;53:750-760.
20. Shah VK, Firmal P, Alam A, Ganguly D, Chattopadhyay S. Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past. Front Immunol 2020;11:1949.
21. Min YQ, Huang M, Sun X, Deng F, Wang H, Ning YJ. Immune evasion of SARS-CoV-2 from interferon antiviral system. Comput Struct Biotechnol J 2021;19:4217-25.
22. Yang Q, Lin F, Wang Y, Zeng M, Luo M. Long Noncoding RNAs as Emerging Regulators of COVID-19. Front Immunol 2021;12:700184.
23. Ouyang J, Hu J, Chen JL. lncRNAs regulate the innate immune response to viral infection. Wiley Interdiscip Rev RNA 2016;7:129-43.
24. Enguita FJ, Leitão AL, McDonald JT, Zaksas V, Das S, Galeano D, et al. The interplay between lncRNAs, RNA-binding proteins and viral genome during SARS-CoV-2 infection reveals strong connections with regulatory events involved in RNA metabolism and immune response. Theranostics 2022;12:3946-3962.
25. Lin Y, Sun Q, Zhang B, Zhao W, Shen C. The regulation of lncRNAs and miRNAs in SARS-CoV-2 infection. Front Cell Dev Biol 2023;11:1229393.
26. Ginn L, La Montagna M, Wu Q, Shi L. Diverse roles of long non-coding RNAs in viral diseases. Rev Med Virol 2021;31:e2198.
27. Heydari R, Tavassolifar MJ, Fayazzadeh S, Sadatpour O, Meyfour A. Long non-coding RNAs in biomarking COVID-19: a machine learning-based approach. Virol J 2024;21:134.
28. Huang K, Wang C, Vagts C, Raguveer V, Finn PW, Perkins DL. Long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 are differentially expressed in severe COVID-19 patients: An integrated single cell analysis. PLoS One 2022;17:e0261242.
29. Martinez-Castillo M, M Elsayed A, López-Berestein G, Amero P, Rodríguez-Aguayo C. An Overview of the Immune Modulatory Properties of Long Non-Coding RNAs and Their Potential Use as Therapeutic Targets in Cancer. Noncoding RNA 2023;9:70.
| Files | ||
| Issue | Vol 64 No 6 (2026) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/acta.v64i6.22315 | |
| Keywords | ||
| COVID-19 Interleukin-12 (IL-12) Interferon-alpha Interferon-gamma Tumor necrosis factor-alpha Long non-coding RNA (lncRNA) Glucokinase 1 (GCK1) | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
pourmohammad M, Khayatzadeh J, Salahi Shamir A, Tehranipour M. The Immunomodulatory Role of Glucokinase 1 (GCK1) lncRNA in Patients With COVID-19. Acta Med Iran. 2026;64(6):333-340.
