Evaluation of miR-let-7f, miR-125a, and miR-125b expression levels in sputum and serum samples of Iranians and Afghans with pulmonary tuberculosis
Abstract
Background and Objectives: The role of microRNAs (miRNAs) in tuberculosis infection is well established. As microRNAs are able to change expression profiles according to different conditions, they can be useful biomarkers. Iranians and Afghans with tuberculosis were studied for three immune-related miRNAs (miR-let-7f, miR-125a, and miR-125b).
Materials and Methods: A total of 60 Iranian and Afghan patients with active pulmonary TB were enrolled in the Pulmonary Department of the Pasteur Institute of Iran. Serum and sputum samples were collected simultaneously from all participants. A Real-time PCR was conducted to detect differentially expressed miRNAs.
Results: Iranian (P<0.0001) and Afghan (P<0.0001) serum samples and Afghan (P<0.0001) sputum samples overexpressed miR-125a, whereas Iranian sputum samples showed downregulation (P=0.0039). In both Iranian (P<0.0001; P=0.0007) and Afghan (P<0.0001; P<0.0001) serum and sputum samples, miR-125b was overexpressed. Furthermore, miR-let-7f downregulation was observed in serum and sputum samples (P<0.0001), whereas Iranian sputum samples had no statistically significant differences (P=0.348).
Conclusion: Overexpression of miR-125a and miR-125b has been detected in Iranian and Afghan samples. In both races, miR-let-7f downregulation has been confirmed. Identification of miRNA profiles under different conditions opens the door to evaluating potential new biomarkers for diagnosis, disease monitoring, and therapeutic markers in TB infection.
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11. Kim JK, Yuk JM, Kim SY, Kim TS, Jin HS, Yang CS, et al. MicroRNA-125a inhibits autophagy activation and antimicrobial responses during mycobacterial infection. J Immunol 2015; 194: 5355-5365.
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21. Liu F, Chen J, Wang P, Li H, Zhou Y, Liu H, et al. MicroRNA-27a controls the intracellular survival of Mycobacterium tuberculosis by regulating calcium-associated autophagy. Nat Commun 2018; 9: 4295.
22. Ouimet M, Koster S, Sakowski E, Ramkhelawon B, Van Solingen C, Oldebeken S, et al. Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism. Nat Immunol 2016; 17: 677-686.
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24. Niu W, Sun B, Li M, Cui J, Huang J, Zhang L. TLR-4/microRNA-125a/NF-κB signaling modulates the immune response to Mycobacterium tuberculosis infection. Cell Cycle 2018; 17: 1931-1945.
25. Zhang K, Huang Q, Deng S, Yang Y, Li J, Wang S. Mechanisms of TLR4-mediated autophagy and nitroxidative stress. Front Cell Infect Microbiol 2021; 11: 766590.
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27. Guio H, Aliaga-Tobar V, Galarza M, Pellon-Cardenas O, Capristano S, Gomez HL, et al. Comparative profiling of circulating exosomal small RNAs derived from peruvian patients with tuberculosis and pulmonary adenocarcinoma. Front Cell Infect Microbiol 2022; 12: 909837.
28. Sun X, Liu K, Wang X, Zhang T, Li X, Zhao Y. Diagnostic value of microRNA 125b in peripheral blood mononuclear cells for pulmonary tuberculosis. Mol Med Rep 2021; 23: 249.
29. Rajaram MV, Ni B, Morris JD, Brooks MN, Carlson TK, Bakthavachalu B, et al. Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b. Proc Natl Acad Sci U S A 2011; 108: 17408-17413.
30. Wang L, Xiong Y, Fu B, Guo D, Zaky MY, Lin X, et al. MicroRNAs as immune regulators and biomarkers in tuberculosis. Front Immunol 2022; 13: 1027472.
31. Sengupta S, Pattanaik KP, Mishra S, Sonawane A. Epigenetic orchestration of host immune defences by Mycobacterium tuberculosis. Microbiol Res 2023; 273: 127400.
32. Sinigaglia A, Peta E, Riccetti S, Venkateswaran S, Manganelli R, Barzon L. Tuberculosis-associated microRNAs: from pathogenesis to disease biomarkers. Cells 2020; 9: 2160.
33. Liang S, Ma J, Gong H, Shao J, Li J, Zhan Y, et al. Immune regulation and emerging roles of noncoding RNAs in Mycobacterium tuberculosis infection. Front Immunol 2022; 13: 987018.
34. da Silva MNS, da Veiga Borges Leal DF, Sena C, Pinto P, Gobbo AR, da Silva MB, et al. Association between SNPs in microRNAs and microRNAs-Machinery Genes with Susceptibility of Leprosy in the Amazon Population. Int J Mol Sci 2022; 23: 10628.
35. Jumat MI, Sarmiento ME, Acosta A, Chin KL. Role of non-coding RNAs in tuberculosis and their potential for clinical applications. J Appl Microbiol 2023; 134: lxad104.
36. Wang Z, Xu H, Wei Z, Jia Y, Wu Y, Qi X, et al. The role of non-coding RNA on macrophage modification in tuberculosis infection. Microb Pathog 2020; 149: 104592.
37. Mirzaei R, Babakhani S, Ajorloo P, Ahmadi RH, Hosseini-Fard SR, Keyvani H, et al. The emerging role of exosomal miRNAs as a diagnostic and therapeutic biomarker in Mycobacterium tuberculosis infection. Mol Med 2021; 27: 34.
38. De Bruyn G, Adams GJ, Teeter LD, Soini H, Musser JM, Graviss EA. The contribution of ethnicity to Mycobacterium tuberculosis strain clustering. Int J Tuberc Lung Dis 2001; 5: 633-641.
39. Nahid P, Jarlsberg L, Kato-Maeda M, Segal M, Osmond D, Gagneux S, et al. Interplay of strain and race/ethnicity in the innate immune response to M. tuberculosis. PLoS One 2018; 13(5): e0195392.
40. Dou H-Y, Chen Y-Y, Kou S-C, Su I-J. Prevalence of Mycobacterium tuberculosis strain genotypes in Taiwan reveals a close link to ethnic and population migration. J Formos Med Assoc 2015; 114: 484-488.
41. Karmon AE, Cardozo ER, Rueda BR, Styer AK. MicroRNAs in the development and pathobiology of uterine leiomyomata: does evidence support future strategies for clinical intervention? Hum Reprod Update 2014; 20: 670-687.
42. Pedersen JL, Bokil NJ, Saunders BM. Developing new TB biomarkers, are miRNA the answer? Tuberculosis (Edinb) 2019; 118: 101860.
2. World Health Organization. (2016). World health statistics 2016: monitoring health for the SDGs, sustainable development goals. World Health Organization. https://apps.who.int/iris/handle/10665/206498.
3. Dastani M, Mohammadzadeh A, Mardaneh J, Ahmadi R. Topic analysis and mapping of tuberculosis research using text mining and co-word analysis. Tuberc Res Treat 2022; 2022: 8039046.
4. Vesga JF, Hallett TB, Reid MJ, Sachdeva KS, Rao R, Khaparde S, et al. Assessing tuberculosis control priorities in high-burden settings: a modelling approach. Lancet Glob Health 2019; 7(5): e585-e595.
5. Zahedi Bialvaei A, Asgharzadeh M, Aghazadeh M, Nourazarian M, Samadi Kafil H. Challenges of tuberculosis in Iran. Jundishapur J Microbiol 2017; 10(3): e37866.
6. Tarashi S, Badi SA, Moshiri A, Ebrahimzadeh N, Fateh A, Vaziri F, et al. The inter-talk between Mycobacterium tuberculosis and the epigenetic mechanisms. Epigenomics 2020; 12: 455-469.
7. Wang J, Xiong K, Zhao S, Zhang C, Zhang J, Xu L, et al. Long-term effects of multi-drug-resistant tuberculosis treatment on gut Microbiota and its health consequences. Front Microbiol 2020; 11: 53.
8. Yadav V, Dwivedi VP, Bhattacharya D, Mittal A, Moodley P, Das G. Understanding the host epigenetics in Mycobacterium tuberculosis infection. J Genet Genome Res 2015; 2: 016.
9. Singh M, Yadav V, Das G (2018). Chapter 4 Host Epigenetic Modifications in Mycobacterium tuberculosis Infection: A Boon or Bane. The Value of BCG and TNF in Autoimmunity, 2st ed. Elsevier. pp. 39-55.
10. Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 2005; 37: 766-770.
11. Kim JK, Yuk JM, Kim SY, Kim TS, Jin HS, Yang CS, et al. MicroRNA-125a inhibits autophagy activation and antimicrobial responses during mycobacterial infection. J Immunol 2015; 194: 5355-5365.
12. Liu G, Wan Q, Li J, Hu X, Gu X, Xu S. Silencing miR-125b-5p attenuates inflammatory response and apoptosis inhibition in Mycobacterium tuberculosis-infected human macrophages by targeting DNA damage-regulated autophagy modulator 2 (DRAM2). Cell Cycle 2020; 19: 3182-3194.
13. Kumar M, Sahu SK, Kumar R, Subuddhi A, Maji RK, Jana K, et al. MicroRNA let-7 modulates the immune response to Mycobacterium tuberculosis infection via control of A20, an inhibitor of the NF-κB pathway. Cell Host Microbe 2015; 17: 345-356.
14. Tarashi S, Sakhaee F, Masoumi M, Ghazanfari Jajin M, Siadat SD, Fateh A. Molecular epidemiology of nontuberculous mycobacteria isolated from tuberculosis-suspected patients. AMB Express 2023; 13: 49.
15. Kramer MF. Stem-loop RT-qPCR for miRNAs. Curr Protoc Mol Biol 2011; Chapter 15: Unit 15. 10.
16. Harapan H, Fitra F, Ichsan I, Mulyadi M, Miotto P, Hasan NA, et al. The roles of microRNAs on tuberculosis infection: meaning or myth? Tuberculosis (Edinb) 2013; 93: 596-605.
17. Kathirvel M, Mahadevan S. The role of epigenetics in tuberculosis infection. Epigenomics 2016; 8: 537-549.
18. Huang RS, Gamazon ER, Ziliak D, Wen Y, Im HK, Zhang W, et al. Population differences in microRNA expression and biological implications. RNA Biol 2011; 8: 692-701.
19. Mehrjoo Z, Fattahi Z, Beheshtian M, Mohseni M, Poustchi H, Ardalani F, et al. Distinct genetic variation and heterogeneity of the Iranian population. PLoS Genet 2019; 15(9): e1008385.
20. Zadran SK, Ilyas M, Dawari S. Genetic variants associated with diseases in Afghan population. Mol Genet Genomic Med 2021; 9(5): e1608.
21. Liu F, Chen J, Wang P, Li H, Zhou Y, Liu H, et al. MicroRNA-27a controls the intracellular survival of Mycobacterium tuberculosis by regulating calcium-associated autophagy. Nat Commun 2018; 9: 4295.
22. Ouimet M, Koster S, Sakowski E, Ramkhelawon B, Van Solingen C, Oldebeken S, et al. Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism. Nat Immunol 2016; 17: 677-686.
23. Wang C, Yang S, Liu C-M, Jiang T-T, Chen Z-L, Tu H-H, et al. Screening and identification of four serum miRNAs as novel potential biomarkers for cured pulmonary tuberculosis. Tuberculosis (Edinb) 2018; 108: 26-34.
24. Niu W, Sun B, Li M, Cui J, Huang J, Zhang L. TLR-4/microRNA-125a/NF-κB signaling modulates the immune response to Mycobacterium tuberculosis infection. Cell Cycle 2018; 17: 1931-1945.
25. Zhang K, Huang Q, Deng S, Yang Y, Li J, Wang S. Mechanisms of TLR4-mediated autophagy and nitroxidative stress. Front Cell Infect Microbiol 2021; 11: 766590.
26. Mehta P. MicroRNA research: The new dawn of Tuberculosis. Indian J Tuberc 2021; 68: 321-329.
27. Guio H, Aliaga-Tobar V, Galarza M, Pellon-Cardenas O, Capristano S, Gomez HL, et al. Comparative profiling of circulating exosomal small RNAs derived from peruvian patients with tuberculosis and pulmonary adenocarcinoma. Front Cell Infect Microbiol 2022; 12: 909837.
28. Sun X, Liu K, Wang X, Zhang T, Li X, Zhao Y. Diagnostic value of microRNA 125b in peripheral blood mononuclear cells for pulmonary tuberculosis. Mol Med Rep 2021; 23: 249.
29. Rajaram MV, Ni B, Morris JD, Brooks MN, Carlson TK, Bakthavachalu B, et al. Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b. Proc Natl Acad Sci U S A 2011; 108: 17408-17413.
30. Wang L, Xiong Y, Fu B, Guo D, Zaky MY, Lin X, et al. MicroRNAs as immune regulators and biomarkers in tuberculosis. Front Immunol 2022; 13: 1027472.
31. Sengupta S, Pattanaik KP, Mishra S, Sonawane A. Epigenetic orchestration of host immune defences by Mycobacterium tuberculosis. Microbiol Res 2023; 273: 127400.
32. Sinigaglia A, Peta E, Riccetti S, Venkateswaran S, Manganelli R, Barzon L. Tuberculosis-associated microRNAs: from pathogenesis to disease biomarkers. Cells 2020; 9: 2160.
33. Liang S, Ma J, Gong H, Shao J, Li J, Zhan Y, et al. Immune regulation and emerging roles of noncoding RNAs in Mycobacterium tuberculosis infection. Front Immunol 2022; 13: 987018.
34. da Silva MNS, da Veiga Borges Leal DF, Sena C, Pinto P, Gobbo AR, da Silva MB, et al. Association between SNPs in microRNAs and microRNAs-Machinery Genes with Susceptibility of Leprosy in the Amazon Population. Int J Mol Sci 2022; 23: 10628.
35. Jumat MI, Sarmiento ME, Acosta A, Chin KL. Role of non-coding RNAs in tuberculosis and their potential for clinical applications. J Appl Microbiol 2023; 134: lxad104.
36. Wang Z, Xu H, Wei Z, Jia Y, Wu Y, Qi X, et al. The role of non-coding RNA on macrophage modification in tuberculosis infection. Microb Pathog 2020; 149: 104592.
37. Mirzaei R, Babakhani S, Ajorloo P, Ahmadi RH, Hosseini-Fard SR, Keyvani H, et al. The emerging role of exosomal miRNAs as a diagnostic and therapeutic biomarker in Mycobacterium tuberculosis infection. Mol Med 2021; 27: 34.
38. De Bruyn G, Adams GJ, Teeter LD, Soini H, Musser JM, Graviss EA. The contribution of ethnicity to Mycobacterium tuberculosis strain clustering. Int J Tuberc Lung Dis 2001; 5: 633-641.
39. Nahid P, Jarlsberg L, Kato-Maeda M, Segal M, Osmond D, Gagneux S, et al. Interplay of strain and race/ethnicity in the innate immune response to M. tuberculosis. PLoS One 2018; 13(5): e0195392.
40. Dou H-Y, Chen Y-Y, Kou S-C, Su I-J. Prevalence of Mycobacterium tuberculosis strain genotypes in Taiwan reveals a close link to ethnic and population migration. J Formos Med Assoc 2015; 114: 484-488.
41. Karmon AE, Cardozo ER, Rueda BR, Styer AK. MicroRNAs in the development and pathobiology of uterine leiomyomata: does evidence support future strategies for clinical intervention? Hum Reprod Update 2014; 20: 670-687.
42. Pedersen JL, Bokil NJ, Saunders BM. Developing new TB biomarkers, are miRNA the answer? Tuberculosis (Edinb) 2019; 118: 101860.
| Files | ||
| Issue | Vol 15 No 5 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v15i5.13872 | |
| Keywords | ||
| Mycobacterium tuberculosis; MicroRNA; Sputum; Serum | ||
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How to Cite
1.
Nour Neamatollahi A, Tarashi S, Ebrahimzadeh N, Vaziri F, Zaheri Birgani MA, Aghasadeghi M, Fateh A, Siadat SD, Bouzari S. Evaluation of miR-let-7f, miR-125a, and miR-125b expression levels in sputum and serum samples of Iranians and Afghans with pulmonary tuberculosis. Iran J Microbiol. 2023;15(5):665-673.
