Inter-correlation of lncRNA THRIL with microRNA-34a and microRNA-125b and their relationship with childhood asthma risk, severity, and inflammation

Main Article Content

Xiaoxue Wang
Weina Li
Shixin Sun
Hong An


Childhood asthma, lncRNA THRIL, miR-34a, miR-125b, exacerbation


Background: Long noncoding RNA (lncRNA) THRIL targets microRNA (miR)-34a and miR-125b to modify immunity, inflammation, and respiratory injury. The current study aimed to determine the inter-correlation of lncRNA THRIL with miR-34a and miR-125b and their relationship with childhood asthma risk, severity, and inflammation.

Methods: Exacerbated asthma children (N=65), remissive asthma children (N=65), and healthy controls (N=65) were enrolled in this case-control study. LncRNA THRIL, miR-34a, and miR-125b in peripheral blood mononuclear cells, as well as inflammatory cytokines in serum, were detected by reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively.

Results: LncRNA THRIL was highest in exacerbated asthma children, then in remissive asthma children, and lowest in healthy controls (P<0.001); reversely, miR-34a (P<0.001) and miR-125b (P=0.004) exhibited the opposite treads. LncRNA THRIL (area under curve (AUC)=0.686) and miR-34a (AUC=0.614) could predict exacerbation risk of asthma, while miR-125b failed. Interestingly, lncRNA THRIL was negatively related to miR-34a and miR-125b in exacerbated asthma children and remissive asthma children (all P<0.05) but not in healthy controls (both P>0.05). Specifically, in exacerbated asthma children: lncRNA THRIL is related to increased eosinophil count (P=0.013), immunoglobulin E (P=0.020), tumor necrosis factor-α (P=0.002), interleukin-1β (P=0.004), interleukin-6 (P=0.012), interleukin-17 (P=0.004) and exacerbated severity (P=0.030); Meanwhile, miR-34a and miR-125b linked with decreased levels of most of the above indexes (most P<0.05).

Conclusion: LncRNA THRIL negatively relates to miR-34a and miR-125b, correlate with inflammatory cytokines, and exacerbated the risk and severity of childhood asthma, indicating their potential as biomarkers for childhood asthma management.

Abstract 90 | PDF Downloads 85 HTML Downloads 10 XML Downloads 2


1. Agache I, Eguiluz-Gracia I, Cojanu C, Laculiceanu A, Del Giacco S, Zemelka-Wiacek M, et al. Advances and highlights in asthma in 2021. Allergy. 2021;76(11):3390–407. 10.1111/all.15054

2. Stern J, Pier J, Litonjua AA. Asthma epidemiology and risk factors. Semin Immunopathol. 2020;42(1):5–15. 10.1007/s00281-020-00785-1

3. Guo X, Li Z, Ling W, Long J, Su C, Li J, et al. Epidemiology of childhood asthma in mainland China (1988-2014): a meta-analysis. Allergy Asthma Proc. 2018;39(3):15–29. 10.2500/aap.2018.39.4131

4. Ellie AS, Sun Y, Hou J, Wang P, Zhang Q, Sundell J. Prevalence of childhood asthma and allergies and their associations with perinatal exposure to home environmental factors: a cross-sectional study in Tianjin, China. Int J Environ Res Public Health. 2021;18(8):4131. 10.3390/ijerph18084131

5. Ren J, Xu J, Zhang P, Bao Y. Prevalence and risk factors of asthma in preschool children in Shanghai, China: a cross-sectional study. Front Pediatr. 2021;9:793452. 10.3389/fped.2021

6. Abul MH, Phipatanakul W. Severe asthma in children: evaluation and management. Allergol Int. 2019;68(2):150–7. 10.1016/j.alit.2018.11.007

7. Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, et al. Global Initiative for asthma strategy 2021: executive summary and rationale for key changes. Eur Respir J. 2022;59(1):2102730. 10.1183/13993003.02730-2021

8. Liu Y, Zhao Y, Liu F, Liu L. Effects of physical exercises on pulmonary rehabilitation, exercise capacity, and quality of life in children with asthma: a meta-analysis. Evid Based Complement Alternat Med. 2021;2021:5104102. 10.1155/2021/5104102

9. Peters MC, Mauger D, Ross KR, Phillips B, Gaston B, Cardet JC, et al. Evidence for exacerbation-prone asthma and predictive biomarkers of exacerbation frequency. Am J Respir Crit Care Med. 2020;202(7):973–82. 10.1164/rccm.201909-1813OC

10. Breiteneder H, Peng YQ, Agache I, Diamant Z, Eiwegger T, Fokkens WJ, et al. Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma. Allergy. 2020;75(12):3039–68. 10.1111/all.14582

11. Song J, Liu D, Yin W. lnc-THRIL and miR-125b relate to disease risk, severity, and imbalance of Th1 cells/Th2 cells in allergic rhinitis. Allergol Immunopathol. 2022;50(3):15–23. 10.15586/aei.v50i3.528

12. Medhat E, Ayeldeen G, Ahmed HH, Shaker O, Gheita T, Ashour SS. HOTAIR and THRIL long non coding RNAs and their target genes in rheumatoid arthritis patients. Rep Biochem Mol Biol. 2022;10(4):614–21. 10.52547/rbmb.10.4.697

13. Liang Y, Li H, Gong X, Ding C. Long non-coding RNA THRIL mediates cell growth and inflammatory response of fibroblast-like synoviocytes by activating PI3K/AKT signals in rheumatoid arthritis. Inflammation. 2020;43(3):1044–53. 10.1007/s10753-020-01189-x

14. Chen H, Hu X, Li R, Liu B, Zheng X, Fang Z, et al. LncRNA THRIL aggravates sepsis-induced acute lung injury by regulating miR-424/ROCK2 axis. Mol Immunol. 2020;126:111–9. 10.1016/j.molimm.2020.07.021

15. Wang Y, Fu X, Yu B, Ai F. Long non-coding RNA THRIL predicts increased acute respiratory distress syndrome risk and positively correlates with disease severity, inflammation, and mortality in sepsis patients. J Clin Lab Anal. 2019;33(6):e22882. 10.1002/jcla.22882

16. Deng Y, Luan S, Zhang Q, Xiao Y. Long noncoding RNA THRIL contributes in lipopolysaccharide-induced HK-2 cells injury by sponging miR-34a. J Cell Biochem. 2019:1444–56. 10.1002/jcb.27354

17. Liu G, Wang Y, Zhang M, Zhang Q. Long non-coding RNA THRIL promotes LPS-induced inflammatory injury by down-regulating microRNA-125b in ATDC5 cells. Int Immunopharmacol. 2019;66:354–61. 10.1016/j.intimp.2018.11.038

18. Li W, Wang X, Sun S, An H. Long non-coding RNA colorectal neoplasia differentially expressed correlates negatively with miR-33a and miR-495 and positively with inflammatory cytokines in asthmatic children. Clin Respir J. 2021;15(11):1175–84. 10.1111/crj.13424

19. Liu T, Liu J, Tian C, Wang H, Wen M, Yan M. LncRNA THRIL is upregulated in sepsis and sponges miR-19a to upregulate TNF-alpha in human bronchial epithelial cells. J Inflamm. 2020;17:31. 10.1186/s12950-020-00259-z

20. Ayoub SE, Hefzy EM, Abd El-Hmid RG, Ahmed NA, Khalefa AA, Ali DY, et al. Analysis of the expression profile of long non-coding RNAs MALAT1 and THRIL in children with immune thrombocytopenia. IUBMB Life. 2020;72(9):1941–50. 10.1002/iub.2310

21. Xie J, Huang L, Li X, Li H, Zhou Y, Zhu H, et al. Immunological cytokine profiling identifies TNF-alpha as a key molecule dys-regulated in autistic children. Oncotarget. 2017;8(47):82390–8. 10.18632/oncotarget.19326

22. Ramsahai JM, Hansbro PM, Wark PAB. Mechanisms and management of asthma exacerbations. Am J Respir Crit Care Med. 2019;199(4):423–32. 10.1164/rccm.201810-1931CI

23. Wu H, Zhou X, Wang X, Cheng W, Hu X, Wang Y, et al. miR-34a in extracellular vesicles from bone marrow mesenchymal stem cells reduces rheumatoid arthritis inflammation via the cyclin I/ATM/ATR/p53 axis. J Cell Mol Med. 2021;25(4):1896–910. 10.1111/jcmm.15857

24. Luoreng ZM, Wei DW, Wang XP. MiR-125b regulates inflammation in bovine mammary epithelial cells by targeting the NKIRAS2 gene. Vet Res. 2021;52(1):122. 10.1186/s13567-021-00992-0

25. Wu X, Cheng YL, Matthen M, Yoon A, Schwartz GK, Bala S, et al. Down-regulation of the tumor suppressor miR-34a contributes to head and neck cancer by up-regulating the MET oncogene and modulating tumor immune evasion. J Exp Clin Cancer Res. 2021;40(1):70. 10.1186/s13046-021-01865-2

26. Hart M, Nickl L, Walch-Rueckheim B, Krammes L, Rheinheimer S, Diener C, et al. Wrinkle in the plan: miR-34a-5p impacts chemokine signaling by modulating CXCL10/CXCL11/CXCR3-axis in CD4(+), CD8(+) T cells, and M1 macrophages. J Immunother Cancer. 2020;8(2). 10.1136/jitc-2020-001617

27. Zhang Q, Yu K, Cao Y, Luo Y, Liu Y, Zhao C. miR-125b promotes the NF-kappaB-mediated inflammatory response in NAFLD via directly targeting TNFAIP3. Life Sci. 2021;270:119071. 10.1016/j.lfs.2021.119071