The lncRNA PVT1/miR-423-5p axis is positively correlated with the severity of bronchial asthma

Main Article Content

Ju Qiu
Kai Zhang
Jing Liu
Dianfeng Cao
Ping Gao
Baoling Zhang
Na Zhao
Ruofang Wang
Xinsheng Shi

Keywords

bronchial asthma, LncRNA PVT1, miR-423-5p, receiver operating characteristic curve, serum

Abstract

Bronchial asthma (BA) is a serious problem affecting the quality of life of patients. Long noncoding RNAs (lncRNAs) are involved in BA. This study set out to investigate expressions of PVT1/miR-423-5p in the serum of BA patients and its clinical value on BA diagnosis and evaluation. This study included the same number (N = 100) of patients with BA at remission (BA-R), BA at exacerbation (BA-E), and healthy controls. PVT1 level was increased in BA-R and BA-E patients, and PVT1 level was higher in BA-E patients than BA-R patients. miR-141-3p targeted PVT1. miR-423-5p was downregulated in the serum of BA patients and was negatively correlated with PVT1. Area under ROC curve of PVT1/miR-423-5p axis on BA-R patients was 0.837 with sensitivity 0.74, specificity 0.84, while that of BA-E was 0.974 with sensitivity 0.87 and specificity 0.95. PVT1/miR-423-5p axis was negatively correlated with FEV1/FVC, FEV1% pred, and IL-10, and positively correlated with IgE, TNF-α, and IL-6. PVT1 and PVT1/miR-423-5p axis were associated with increased severity while miR-423-5p axis was negatively associated with BA severity. In conclusion, increased levels of PVT1/miR-423-5p had higher diagnostic efficiency on BA patients, especially patients with acute exacerbation.

Abstract 73 | PDF Downloads 51 HTML Downloads 3 XML Downloads 0

References

1. Huo Y, Zhang HY. Genetic mechanisms of asthma and the implications for drug repositioning. Genes (Basel). 2018 May 3;9(5). 10.3390/genes9050237

2. Lambrecht BN, Hammad H, Fahy JV. The cytokines of asthma. Immunity. 2019 Apr 16;50(4):975–991. 10.1016/j.immuni.2019.03.018

3. Michalik M, Wojcik-Pszczola K, Paw, Wnuk M, Koczurkiewicz D, Sanak P, et al. Fibroblast-to-myofibroblast transition in bronchial asthma. Cell Mol Life Sci. 2018 Nov;75(21):3943–3961. 10.1007/s00018-018-2899-4

4. Upham JW, James LM. Remission of asthma: the next therapeutic frontier? Pharmacol Ther. 2011 Apr;130(1):38–45. 10.1016/j.pharmthera.2011.01.002

5. Maselli DJ, Peters JI. Medication regimens for managing acute asthma. Respir Care. 2018 Jun;63(6):783–796. 10.4187/respcare.05953

6. Al-Busaidi N, Habibulla Z, Bhatnagar M, Al-Lawati N, Al-Mahrouqi Y. The burden of asthma in Oman. Sultan Qaboos Univ Med J. 2015 May;15(2):e184–e190.

7. Croisant S. Epidemiology of asthma: prevalence and burden of disease. Adv Exp Med Biol. 2014;795:17–29. 10.1007/978-1-4614-8603-9_2

8. Narozna B, Langwinski W, Szczepankiewicz A. Non-coding RNAs in pediatric airway diseases. Genes (Basel). 2017 Nov 27;8(12). 10.3390/genes8120348

9. Booton R, Lindsay MA. Emerging role of microRNAs and long noncoding RNAs in respiratory disease. Chest. 2014 Jul;146(1):193–204. 10.1378/chest.13-2736

10. Zhang J, Zhu Y, Wang R. Long noncoding RNAs in respiratory diseases. Histol Histopathol. 2018 Aug;33(8):747–756.

11. Ma L, Zhang Q, Hao J, Wang J, Wang C. LncRNA PVT1 exacerbates the inflammation and cell-barrier injury during asthma by regulating miR-149. J Biochem Mol Toxicol. 2020 Nov;34(11):e22563. 10.1002/jbt.22563

12. Austin PJ, Tsitsiou C, Boardman E, Jones SW, Lindsay MA, Adcock IM, et al. Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle. J Allergy Clin Immunol. 2017 Mar;139(3):780–789. 10.1016/j.jaci.2016.06.014

13. Li S, Ye X, Lu Y. Long non-coding RNA NEAT1 overexpression associates with increased exacerbation risk, severity, and inflammation, as well as decreased lung function through the interaction with microRNA-124 in asthma. J Clin Lab Anal. 2020 Jan;34(1):e23023. 10.1002/jcla.23023

14. Qiu YU, Y Wu, MJ Lin, T Bian, YL Xiao, C Qin. LncRNA-MEG3 functions as a competing endogenous RNA to regulate Treg/Th17 balance in patients with asthma by targeting microRNA-17/RORgammat. Biomed Pharmacother. 2019 Mar;111:386–394. 10.1016/j.biopha.2018.12.080

15. Ye S, Zhu S, Feng L. LncRNA ANRIL/miR-125a axis exhibits potential as a biomarker for disease exacerbation, severity, and inflammation in bronchial asthma. J Clin Lab Anal. 2020 Mar;34(3):e23092. 10.1002/jcla.23092

16. Herbert C, Sebesfi M, Zeng QX, Oliver BG, Foster PS, Kumar rK. Using multiple online databases to help identify microRNAs regulating the airway epithelial cell response to a virus-like stimulus. Respirology. 2015 Nov;20(8):1206–1212. 10.1111/resp.12606

17. Schmittgen TD , Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101–1108. 10.1038/nprot.2008.73

18. Zhang XY, Tang XY, Li N, Zhao LM, Guo Y, Li XS, et al. GAS5 promotes airway smooth muscle cell proliferation in asthma via controlling miR-10a/BDNF signaling pathway. Life Sci. 2018 Nov 1;212:93–101. 10.1016/j.lfs.2018.09.002

19. Toskala E, Kennedy DW. Asthma risk factors. Int Forum Allergy Rhinol. 2015 Sep;5(Suppl 1):S11–S16. 10.1002/alr.21557

20. Li Y, Yin Z, Fan J, Zhang S, Yang W. The roles of exosomal miRNAs and lncRNAs in lung diseases. Signal Transduct Target Ther. 2019;4:47. 10.1038/s41392-019-0080-7

21. Del Giacco S, Bakirtas R, Bel A, Custovic E, Diamant A, Hamelmann E, et al. Allergy in severe asthma. Allergy. 2017 Feb;72(2):207–220. 10.1111/all.13072

22. Chae EJ, Kim TB, Cho YS, Park CS, Seo JB, Kim N, et al. Airway measurement for airway remodeling defined by post-bronchodilator FEV1/FVC in asthma: investigation using inspiration-expiration computed tomography. Allergy Asthma Immunol Res. 2011 Apr;3(2):111–117. 10.4168/aair.2011.3.2.111

23. Bazan-Socha S, Mastalerz L, Cybulska A, Zareba L, Kremers R, Zabczyk M, et al. Prothrombotic state in asthma is related to increased levels of inflammatory cytokines, IL-6 and TNFalpha, in peripheral blood. Inflammation. 2017 Aug;40(4):1225–1235. 10.1007/s10753-017-0565-x

24. Branchett WJ, Stolting H, Oliver RA, Walker SA, Puttur F, Gregory LG, et al. A T cell-myeloid IL-10 axis regulates pathogenic IFN-gamma-dependent immunity in a mouse model of type 2-low asthma. J Allergy Clin Immunol. 2020 Feb;145(2):666–678, e669. 10.1016/j.jaci.2019.08.006

25. Wei, Han, Dai, Guo, Zhang, Zhao, et al., Exposure to ozone impacted Th1/Th2 imbalance of CD(4+) T cells and apoptosis of ASMCs underlying asthmatic progression by activating lncRNA PVT1-miR-15a-5p/miR-29c-3p signaling. Aging (Albany NY). 2020 Nov 20;12(24):25229–25255. 10.18632/aging.104124

26. Wang Y, Luo B, Zhang W, Zhu S, Chen C, Zhou L. The lncRNA PVT1/miR-590-5p/FSTL1 axis modulates the proliferation and migration of airway smooth muscle cells in asthma. Autoimmunity. 2021 May;54(3):138–147. 10.1080/08916934.2021.1897977

27. Lin QI, Qi QL, Hou S, Chen Z, Zhang L, Zhao HG, et al. LncRNA PVT1 acts as a tumor promoter in thyroid cancer and promotes tumor progression by mediating miR-423-5p-PAK3. Cancer Manag Res. 2020;12:13403–13413. 10.2147/CMAR.S283443