Diagnostic value of microRNA‑125b in peripheral blood mononuclear cells for pulmonary tuberculosis

Sun,Xiaolu; Liu,Kai; Wang,Xinhong; Zhang,Tianhua; Li,Xiaomou; Zhao,Yan

doi:10.3892/mmr.2021.11888

Diagnostic value of microRNA‑125b in peripheral blood mononuclear cells for pulmonary tuberculosis

Authors:
- Xiaolu Sun
- Kai Liu
- Xinhong Wang
- Tianhua Zhang
- Xiaomou Li
- Yan Zhao
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Affiliations: Department of Tuberculosis Treatment and Prevention, Shaanxi Provincial Institute for Tuberculosis Control and Prevention, Xi'an, Shaanxi 710048, P.R. China, Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department II of Tuberculosis Treatment, Tuberculosis Prevention and Control Hospital of Shaanxi Provincial, Xi'an, Shaanxi 710100, P.R. China, Department of Tuberculosis Treatment, Shaanxi Provincial Institute for Tuberculosis Control and Prevention, Xi'an, Shaanxi 710048, P.R. China
Published online on: February 1, 2021 https://doi.org/10.3892/mmr.2021.11888
Article Number: 249

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Abstract

Pulmonary tuberculosis (TB) is a chronic respiratory infectious disease. Certain microRNAs (miRNAs or miRs) are reported to be involved in regulating TB progression. The present study aimed to evaluate the diagnostic potential of miR‑125b in pulmonary TB. The expression levels of miR‑125b and Raf1 proto‑oncogene serine/threonine protein kinase (RAF1) were analyzed via reverse transcription‑quantitative (RT‑q)PCR in patients with TB. The correlation between miR‑125b and the clinical indicators was investigated, and a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR‑125b. The relationship between miR‑125b and RAF1 was examined using the dual luciferase reporter gene assay. IL‑6, TNF‑α, NF‑κB and IFN‑γ levels were detected using ELISA kits, and then the correlation between miR‑125b expression and the levels of IL‑6, TNF‑α, NF‑κB, IFN‑γ and RAF1 in peripheral blood mononuclear cells (PBMCs) was analyzed. Moreover, RAF1 mRNA and protein expression levels were detected via RT‑qPCR and western blotting. The results demonstrated that miR‑125b expression was decreased in patients with TB, while RAF1 expression was increased. Furthermore, miR‑125b expression was associated with sputum acid‑fast bacillus smear. The area under the ROC curve of miR‑125b was 0.9413, and the sensitivity and specificity of miR‑125b expression for TB were 90 and 92.5%, respectively. IL‑6, TNF‑α, NF‑κB and IFN‑γ levels were negatively correlated with miR‑125b expression, and were inhibited by miR‑125b in PBMCs. Moreover, miR‑125b targeted RAF1 to negatively regulate its expression levels. RAF1 reversed the role of miR‑125b in attenuating IL‑6, TNF‑α, NF‑κB and IFN‑γ levels in PBMCs. The present study demonstrated that the levels of IL‑6, TNF‑α, NF‑κB and IFN‑γ were negatively correlated with miR‑125b expression in PBMCs. Thus, it was suggested that miR‑125b served important roles in the occurrence and development of TB by decreasing the levels of IL‑6, TNF‑α, NF‑κB and IFN‑γ by inhibiting RAF1.

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1	Giorgia S, Alberto R, Alberto M and Raviglione MC: Tuberculosis: Epidemiology and control. Mediterr J Hematol Infect Dis. 6:e20140702014. View Article : Google Scholar : PubMed/NCBI
2	World Health Organization (WHO), . Global tuberculosis report 2018. WHO; Geneva: 2018
3	Ndzi EN, Nkenfou CN, Mekue LM, Zentilin L, Tamgue O, Pefura EWY, Kuiaté JR, Giacca M and Ndjolo A: MicroRNA hsa-miR-29a-3p is a plasma biomarker for the differential diagnosis and monitoring of tuberculosis. Tuberculosis (Edinb). 114:69–76. 2019. View Article : Google Scholar : PubMed/NCBI
4	Small PM: Tuberculosis: A new vision for the 21st century. Kekkaku. 84:721–726. 2009.PubMed/NCBI
5	Heydari AA, Movahhede Danesh MR and Ghazvini K: Urine PCR evaluation to diagnose pulmonary tuberculosis. Jundishapur J Microbiol. 7:e93112014. View Article : Google Scholar : PubMed/NCBI
6	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
7	Macfarlane LA and Murphy PR: MicroRNA: Biogenesis, function and role in cancer. Curr Genomics. 11:537–561. 2010. View Article : Google Scholar : PubMed/NCBI
8	Harapan H, Fitra F, Ichsan I, Mulyadi M, Miotto P, Hasan NA, Calado M and Cirillo DM: The roles of microRNAs on tuberculosis infection: Meaning or myth? Tuberculosis (Edinb). 93:596–605. 2013. View Article : Google Scholar : PubMed/NCBI
9	Spinelli SV, Diaz A, D'Attilio L, Marchesini MM, Bogue C, Bay ML and Bottasso OA: Altered microRNA expression levels in mononuclear cells of patients with pulmonary and pleural tuberculosis and their relation with components of the immune response. Mol Immunol. 53:265–269. 2013. View Article : Google Scholar : PubMed/NCBI
10	Qi Y, Cui L, Ge Y, Shi Z, Zhao K, Guo X, Yang D, Yu H, Cui L, Shan Y, et al: Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection. BMC Infect Dis. 12:3842012. View Article : Google Scholar : PubMed/NCBI
11	Furci L, Schena E, Miotto P and Cirillo DM: Alteration of human macrophages microRNA expression profile upon infection with mycobacterium tuberculosis. Int J Mycobacteriol. 2:128–134. 2013. View Article : Google Scholar : PubMed/NCBI
12	Tu H, Yang S, Jiang T, Wei L, Shi L, Liu C, Wang C, Huang H, Hu Y, Chen Z, et al: Elevated pulmonary tuberculosis biomarker miR-423-5p plays critical role in the occurrence of active TB by inhibiting autophagosome-lysosome fusion. Emerg Microbes Infect. 8:448–460. 2019. View Article : Google Scholar : PubMed/NCBI
13	Fu X, Zeng L, Liu Z, Ke X, Lei L and Li G: MicroRNA-206 regulates the secretion of inflammatory cytokines and MMP9 expression by targeting TIMP3 in mycobacterium tuberculosis-infected THP-1 human macrophages. Biochem Biophys Res Commun. 477:167–173. 2016. View Article : Google Scholar : PubMed/NCBI
14	Wang JX, Xu J, Han YF, Zhu YB and Zhang WJ: Diagnostic values of microRNA-31 in peripheral blood mononuclear cells for pediatric pulmonary tuberculosis in Chinese patients. Genet Mol Res. 14:17235–17243. 2015. View Article : Google Scholar : PubMed/NCBI
15	No authors listed, . Diagnostic Standards and Classification of Tuberculosis in Adults and Children. This official statement of the American Thoracic Society and the Centers for Disease Control and Prevention was adopted by the ATS Board of Directors, July 1999. This statement was endorsed by the Council of the Infectious Disease Society of America, September 1999. Am J Respir Crit Care Med. 161((4 Pt 1)): 1376–1395. 2000.PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
17	Wang C, Yang S, Liu CM, Jiang TT, Chen ZL, Tu HH, Mao LG, Li ZJ and Li JC: Screening and identification of four serum miRNAs as novel potential biomarkers for cured pulmonary tuberculosis. Tuberculosis (Edinb). 108:26–34. 2018. View Article : Google Scholar : PubMed/NCBI
18	Zhang X, Guo J, Fan S, Li Y, Wei L, Yang X, Jiang T, Chen Z, Wang C, Liu J, et al: Screening and identification of six serum microRNAs as novel potential combination biomarkers for pulmonary tuberculosis diagnosis. PLoS One. 8:e810762013. View Article : Google Scholar : PubMed/NCBI
19	Bloom BM, Grundling J, Bestwick JP and Harris T: The role of venous blood gas in the emergency department: A systematic review and meta-analysis. Eur J Emerg Med. 21:81–88. 2014. View Article : Google Scholar : PubMed/NCBI
20	Wang C, Yang S, Sun G, Tang X, Lu S, Neyrolles O and Gao Q: Comparative miRNA expression profiles in individuals with latent and active tuberculosis. PLoS One. 6:e258322011. View Article : Google Scholar : PubMed/NCBI
21	Kleinsteuber K, Heesch K, Schattling S, Kohns M, Sander-Jülch C, Walzl G, Hesseling A, Mayatepek E, Fleischer B, Marx FM and Jacobsen M: Decreased expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4(+) T cells and peripheral blood from tuberculosis patients. PLoS One. 8:e616092013. View Article : Google Scholar : PubMed/NCBI
22	Liu Y, Wang R, Jiang J, Yang B, Cao Z and Cheng X: miR-223 is upregulated in monocytes from patients with tuberculosis and regulates function of monocyte-derived macrophages. Mol Immunol. 67:475–481. 2015. View Article : Google Scholar : PubMed/NCBI
23	Wagh V, Urhekar A and Modi D: Levels of microRNA miR-16 and miR-155 are altered in serum of patients with tuberculosis and associate with responses to therapy. Tuberculosis (Edinb). 102:24–30. 2017. View Article : Google Scholar : PubMed/NCBI
24	Wang HL, Li YX, Niu YT, Zheng J, Wu J, Shi GJ, Ma L, Niu Y, Sun T and Yu JQ: Observing anti-inflammatory and anti-nociceptive activities of glycyrrhizin through regulating COX-2 and pro-inflammatory cytokines expressions in mice. Inflammation. 38:2269–2278. 2015. View Article : Google Scholar : PubMed/NCBI
25	Wang C, Ning LP, Wang YH, Zhang Y, Ding XL, Ge HY, Arendt-Nielsen L and Yue SW: Nuclear factor-kappa B mediates TRPV4-NO pathway involved in thermal hyperalgesia following chronic compression of the dorsal root ganglion in rats. Behav Brain Res. 221:19–24. 2011. View Article : Google Scholar : PubMed/NCBI
26	Feng FM, Liu XX, Sun YH, Zhang P, Sun SF, Zhang B, Wang XT and Lu LJ: Independent and joint effects of the IL-6 and IL-10 gene polymorphisms in pulmonary tuberculosis among the Chinese Han population. Genet Mol Res. 13:7766–7772. 2014. View Article : Google Scholar : PubMed/NCBI
27	Yang CS, Lee HM, Lee JY, Kim JA, Lee SJ, Shin DM, Lee YH, Lee DS, El-Benna J and Jo EK: Reactive oxygen species and p47phox activation are essential for the mycobacterium tuberculosis-induced pro-inflammatory response in murine microglia. J Neuroinflammation. 4:272007. View Article : Google Scholar : PubMed/NCBI
28	Afum-Adjei Awuah A, Ueberberg B, Owusu-Dabo E, Frempong M and Jacobsen M: Dynamics of T-cell IFN-γ and miR-29a expression during active pulmonary tuberculosis. Int Immunol. 26:579–582. 2014. View Article : Google Scholar : PubMed/NCBI
29	Ribera E, Ocana I, Martinez-Vazquez JM, Rossell M, Espanol T and Ruibal A: High level of interferon gamma in tuberculous pleural effusion. Chest. 93:308–311. 1988. View Article : Google Scholar : PubMed/NCBI
30	Dutta RK, Kathania M, Raje M and Majumdar S: IL-6 inhibits IFN-γ induced autophagy in mycobacterium tuberculosis H37Rv infected macrophages. Int J Biochem Cell Biol. 44:942–954. 2012. View Article : Google Scholar : PubMed/NCBI
31	Song Q, Li H, Shao H, Li C and Lu X: MicroRNA-365 in macrophages regulates mycobacterium tuberculosis-induced active pulmonary tuberculosis via interleukin-6. Int J Clin Exp Med. 8:15458–15465. 2015.PubMed/NCBI
32	Ma C, Li Y, Li M, Deng G, Wu X, Zeng J, Hao X, Wang X, Liu J, Cho WCS, et al: microRNA-124 negatively regulates TLR signaling in alveolar macrophages in response to mycobacterial infection. Mol Immunol. 62:150–158. 2014. View Article : Google Scholar : PubMed/NCBI
33	Huang Z, Zheng D, Pu J, Dai J, Zhang Y, Zhang W and Wu Z: MicroRNA-125b protects liver from ischemia/reperfusion injury via inhibiting TRAF6 and NF-κB pathway. Biosci Biotechnol Biochem. 83:829–835. 2019. View Article : Google Scholar : PubMed/NCBI
34	Xiao T, Zhou Y, Li H, Xiong L, Wang J, Wang ZH and Liu LH: MiR-125b suppresses the carcinogenesis of osteosarcoma cells via the MAPK-STAT3 pathway. J Cell Biochem. 2018.(Epub ahead of print).
35	Tian H, Yin L, Ding K, Xia YY, Wang XH, Wu JZ and He X: Raf1 is a prognostic factor for progression in patients with nonsmall cell lung cancer after radiotherapy. Oncol Rep. 39:1966–1974. 2018.PubMed/NCBI
36	Baumann B, Weber CK, Troppmair J, Whiteside S, Israel A, Rapp UR and Wirth T: Raf induces NF-kappaB by membrane shuttle kinase MEKK1, a signaling pathway critical for transformation. Proc Natl Acad Sci USA. 97:4615–4620. 2000. View Article : Google Scholar : PubMed/NCBI