Original Article

Role of Long Non-coding RNA HSD17B3-AS1 in Trauma for COVID-19


COVID-19, an acute respiratory syndrome caused by the SARS-CoV-2 virus, was first reported in late 2019 in Wuhan, China, and rapidly escalated into a global pandemic. The condition can lead to organ dysfunction and ultimately death through its onset of acute respiratory distress syndrome (ARDS). Disease severity has been linked to proinflammatory cytokines which activate the NF-κB and STAT transcription factors in infected cells. It has been proven that lncRNAs play a very important role in reducing or increasing inflammatory factors. This makes them potentially valuable in recognizing pathogenesis pathways and therapeutic targets in COVID-19. Nanocurcumin is known as an antioxidant, tumor suppressor and anti-inflammatory substance, and it can be effective to reduce inflammation caused by the disease of COVID-19.
This study analyzed Sequence Read Archive data from COVID-19 patients with acute versus milder symptoms, identifying dysregulated genes and non-coding RNAs. To verify this correlation, the expression of the candidate gene was evaluated with quantitative polymerase chain reaction (qPCR) in mouse models, while immunoglobulin (Ig) G titer was measured using enzyme-linked immunosorbent assay (ELISA) in mouse serum samples.
Here we introduced a novel lncRNA called HSD17B3-AS1, suggested as a therapeutic target in COVID-19 patients with acute symptoms. Furthermore, we revealed nanocurcumin is reducing the expression of HSD17B3-AS1 which leads to reduced inflammation in mice.
These results suggest that HSD17B3-AS1 plays a significant regulatory role in managing COVID-19, and the downregulation of HSD17B3-AS1 by Nanocurcumin presents a promising treatment option for minimizing complications in COVID-19 patients.

1. Ciotti M, Ciccozzi M, Terrinoni A, Jiang W-C, Wang C-B, Bernardini S. The COVID-19 pandemic. Critical reviews in clinical laboratory sciences. 2020;57(6):365-88.
2. Wu D, Wu T, Liu Q, Yang Z. The SARS-CoV-2 outbreak: what we know. Int J Infect Dis. 2020;94:44-8.
3. Tu Y-F, Chien C-S, Yarmishyn AA, Lin Y-Y, Luo Y-H, Lin Y-T, et al. A review of SARS-CoV-2 and the ongoing clinical trials. Int J Mol Sci 2020;21(7):2657.
4. Martellucci CA, Flacco ME, Cappadona R, Bravi F, Mantovani L, Manzoli L. SARS-CoV-2 pandemic: An overview. Advances in biological regulation. 2020;77:100736.
5. Jourdes A, Lafaurie M, Martin-Blondel G, Delobel P, Faruch M, Charpentier S, et al. Clinical characteristics and outcome of hospitalized patients with SARS-CoV-2 infection at Toulouse University hospital (France). Results from the Covid-clinic-Toul cohort. La Revue de médecine interne. 2020;41(11):732-40.
6. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. lancet. 2020;395(10229):1054-62.
7. Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LF. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363-74.
8. Henderson LA, Canna SW, Schulert GS, Volpi S, Lee PY, Kernan KF, et al. On the alert for cytokine storm: immunopathology in COVID‐19. Arthritis Rheumatol. 2020;72(7):1059-63.
9. Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Inves. 2020;130(5):2620-9.
10. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. lancet. 2020;395(10223):507-13.
11. Hirano T, Murakami M. COVID-19: a new virus, but a familiar receptor and cytokine release syndrome. Immunity. 2020;52(5):731-3.
12. Mahmudpour M, Roozbeh J, Keshavarz M, Farrokhi S, Nabipour I. COVID-19 cytokine storm: The anger of inflammation. Cytokine. 2020;133:155151.
13. McGonagle D, Sharif K, O'Regan A, Bridgewood C. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmunity Rev. 2020;19(6):102537.
14. Yang L, Xie X, Tu Z, Fu J, Xu D, Zhou Y. The signal pathways and treatment of cytokine storm in COVID-19. Signal transduction and targeted therapy. 2021;6(1):1-20.
15. Heward JA, Lindsay MA. Long non-coding RNAs in the regulation of the immune response. Trends Immunol. 2014;35(9):408-19.
16. Hadjicharalambous MR, Lindsay MA. Long non-coding RNAs and the innate immune response. Non-coding RNA. 2019;5(2):34.
17. Ma S, Ming Z, Gong A-Y, Wang Y, Chen X, Hu G, et al. A long noncoding RNA, lincRNA‐Tnfaip3, acts as a coregulator of NF‐κB to modulate inflammatory gene transcription in mouse macrophages. FASEB J. 2017;31(3):1215-25.
18. Valkov E, Muthukumar S, Chang C-T, Jonas S, Weichenrieder O, Izaurralde E. Structure of the Dcp2–Dcp1 mRNA-decapping complex in the activated conformation. Nat Structural Mol Biol. 2016;23(6):574-9.
19. Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014;505(7483):344-52.
20. Lin M, Xia B, Qin L, Chen H, Lou G. S100A7 regulates ovarian cancer cell metastasis and chemoresistance through MAPK signaling and is targeted by miR-330-5p. DNA and cell biology. 2018;37(5):491-500.
21. Xu K, Hu W, Leskovec J, Jegelka S. How powerful are graph neural networks? arXiv preprint arXiv:181000826. 2018.
22. Rahimzadeh M, Sadeghizadeh M, Najafi F, Arab SS, Pourhosseini PS. Application of a novel pH-responsive gemini surfactant for delivery of curcumin molecules. Materials Res Express. 2020;7(6):065403.
23. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-42.
24. Hu B, Huang S, Yin L. The cytokine storm and COVID‐19. J Med Virol. 2021;93(1):250-6.
25. Haider A, Faheem M, Jamal SB, Naeem M, Khalil AAK, Khan R. The Pathophysiology of Repurposed Antiviral Drugs for treatment of COVID-19 Infection. Life Sci. 2020;1(supplement):6-.
26. Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M, et al. How COVID-19 induces cytokine storm with high mortality. Inflammation and regeneration. 2020;40(1):1-7.
27. Kornienko AE, Guenzl PM, Barlow DP, Pauler FM. Gene regulation by the act of long non-coding RNA transcription. BMC biology. 2013;11(1):1-14.
28. O'Brien J, Hayder H, Zayed Y, Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol. 2018;9:402.
29. Rabaan AA, Al-Ahmed SH, Garout MA, Al-Qaaneh AM, Sule AA, Tirupathi R, et al. Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses. Pathogens. 2021;10(5):565.
30. Qiao J, Li W, Bao J, Peng Q, Wen D, Wang J, et al. The expression of SARS-CoV-2 receptor ACE2 and CD147, and protease TMPRSS2 in human and mouse brain cells and mouse brain tissues. Biochem Biophys Res Commun. 2020;533(4):867-71.
31. Nersisyan S, Engibaryan N, Gorbonos A, Kirdey K, Makhonin A, Tonevitsky A. Potential role of cellular miRNAs in coronavirus-host interplay. PeerJ. 2020;8:e9994.
32. Chen L-J, Xu R, Yu H-M, Chang Q, Zhong J-C. The ACE2/apelin signaling, microRNAs, and hypertension. Int J Hypertension. 2015;2015.
33. Niu W, Wu F, Cui H, Cao W, Chao Y, Wu Z, et al. Network pharmacology analysis to identify phytochemicals in traditional Chinese medicines that may regulate ACE2 for the treatment of COVID-19. Evidence-Based Complementary and Alternative Medicine. 2020;2020.
34. Serpeloni JM, Neto QAL, Lucio LC, Ramao A, de Oliveira JC, Gradia DF, et al. Genome interaction of the virus and the host genes and non-coding RNAs in SARS-CoV-2 infection. Immunobiology. 2021;226(5):152130.
35. Bao M-H, Szeto V, Yang BB, Zhu S-z, Sun H-S, Feng Z-P. Long non-coding RNAs in ischemic stroke. Cell Death Dis. 2018;9(3):1-12.
36. Morenikeji OB, Bernard K, Strutton E, Wallace M, Thomas BN. Evolutionarily conserved long non-coding RNA regulates gene expression in cytokine storm during COVID-19. Front Bioengineer Biotechnol. 2021;8:1330.
37. Asadirad A, Nashibi R, Khodadadi A, Ghadiri AA, Sadeghi M, Aminian A, et al. Antiinflammatory potential of nano‐curcumin as an alternative therapeutic agent for the treatment of mild‐to‐moderate hospitalized COVID‐19 patients in a placebo‐controlled clinical trial. Phytotherapy Res. 2022;36(2):1023-31.
38. Tahmasebi S, El‐Esawi MA, Mahmoud ZH, Timoshin A, Valizadeh H, Roshangar L, et al. Immunomodulatory effects of Nanocurcumin on Th17 cell responses in mild and severe COVID‐19 patients. J Cell Physiol. 2021;236(7):5325-38.
IssueVol 22 No 4 (2023) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijaai.v22i4.13607
COVID-19 Long non-coding RNA Trauma

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Javanmard A-R, Esmaeili Gouvarchinghaleh H, Dorostkar R, Tat M. Role of Long Non-coding RNA HSD17B3-AS1 in Trauma for COVID-19. Iran J Allergy Asthma Immunol. 2023;22(4):345-353.