Analysis of miR-21-5p and miR-144-5p expression as biomarkers in active lung tuberculosis and home contacts

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APRILIA PITUT SAVITRI
MUHAMMAD NASRUM MASSI
MOCHAMMAD HATTA
ARIF SANTOSO
MUHAMMAD FACHRI
IRAWATY DJAHARUDDIN
SITTI WAHYUNI
MUHAMMAD ILYAS
HARUN ISKANDAR
ILHAMJAYA PATELLONGI
IRDA HANDAYANI
ISRAINI WIYULANDA ISKANDAR
NAJDAH HIDAYAH
NIRMAWATI ANGRIA
HANDAYANI HALIK

Abstract

Abstract. Savitri AP, Massi MN, Hatta M, Santoso A, Fachri M, Djaharuddin I, Wahyuni S, Ilyas M, Iskandar H, Pattelongi I, Handayani I, Iskandar IW, Hidayah N, Angria N, Halik H. 2025. Analysis of miR-21-5p and miR-144-5p expression as biomarkers in active lung tuberculosis and home contacts. Biodiversitas 26: 831-836. Considering the central role of microRNAs (miRNAs) in development and disease, researchers have proposed that specific circulating miRNAs affect the outcome of tuberculosis (TB) infection and that blood miRNA levels might reflect the course of the disease. This study analyzed the expression of miR-21-5p and miR-144-5p as potential biomarkers in patients with active TB and their household contacts (individuals with latent TB and healthy contacts). This study used a cross-sectional design and enrolled 20 people with active TB, 22 household contacts with positive interferon-gamma release assay results, and 22 healthy controls. miR-21-5p and miR-144-5p expression was examined using quantitative real-time PCR. miR-21-5p expression was more than 37-fold higher in patients with active TB than in healthy contacts. Meanwhile, miR-21-5p expression was approximately 15-fold higher in patients with active TB than in those with latent TB. miR-21-5p expression was 2.5-fold higher in patients with latent TB than in healthy contacts, whereas miR-144-5p expression was 35-fold higher in patients with active TB than in healthy contacts, and approximately 52-fold higher in patients with active TB than in contacts with latent TB. miR-144-5p expression in latent TB was approximately 1.5-fold higher in healthy contacts than in contacts with latent TB. Receiver operating characteristic analysis illustrated that miR-21-5p and miR-144-5p could distinguish latent TB from active TB with areas under the curve of 0.811 (95% Confidence Interval (CI) = 0.67-0.953) and 0.818 (95% CI = 0.689-0.947), respectively. miR-21-5p and miR-144-5p expression was elevated in active TB, highlighting their potential as diagnostic biomarkers.

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References
Angria N, Massi MN, Bukhari A, Djaharuddin I, Jumadi O, Ahmad A, Miskad UA, Ladju RB, Santoso A, Halik H. 2022. Expression of miRNA-29a-3p and IFN-? as biomarkers in active and latent pulmonary tuberculosis. Ann Med Surg 83: 104786. DOI: 10.1016/j.amsu.2022.104786.
Bautista-Sánchez D, Arriaga-Canon C, Pedroza-Torres A, De La Rosa-Velázquez IA, González-Barrios R, Contreras-Espinosa L, Montiel-Manríquez R, Castro-Hernández C, Fragoso-Ontiveros V, Álvarez-Gómez RM, Herrera LA. 2020. The promising role of miR-21 as a cancer biomarker and its importance in RNA-based therapeutics. Mol Ther Nucleic Acids 20: 409-420. DOI: 10.1016/j.omtn.2020.03.003.
Behrouzi A, Alimohammadi M, Nafari AH, Yousefi MH, Rad FR, Vaziri F, Siadat SD. 2019. The role of host mirnas on Mycobacterium tuberculosis. ExRNA 1: 40. DOI: 10.1186/s41544-019-0040-y.
Daniel EA, Sathiyamani B, Thiruvengadam K, Vivekanandan S, Vembuli H, Hanna LE. 2022. MicroRNAs as diagnostic biomarkers for tuberculosis: A systematic review and meta- analysis. Front Immunol 13: 954396. DOI: 10.3389/fimmu.2022.954396.
Fachri M, Hatta M, Abadi S, Santoso SS, Wikanningtyas TA, Syarifuddin A, Dwiyanti R, Noviyanthi RA. 2018. Comparison of Acid Fast Bacilli (AFB) smear for Mycobacterium tuberculosis on adult pulmonary Tuberculosis (TB) patients with type 2 Diabetes Mellitus (DM) and without type 2 DM. Respir Med Case Rep 23: 158-162. DOI: 10.1016/j.rmcr.2018.02.008.
Flynn JL, Chan J. 2001. Tuberculosis: Latency and reactivation. Infect Immun 69 (7): 4195-4201. DOI: 10.1128/IAI.69.7.4195-4201.2001.
Hatta M, Sultan AR, Tandirogang N, Masjudi, Yadi. 2010. Detection and identification of mycobacteria in sputum from suspected tuberculosis patients. BMC Res Notes 3: 72. DOI: 10.1186/1756-0500-3-72.
Liu Y, Wang X, Jiang J, Cao Z, Yang B, Cheng X. 2011. Modulation of T cell cytokine production by miR-144* with elevated expression in patients with pulmonary tuberculosis. Mol Immunol 48 (9-10): 1084-1090. DOI: 10.1016/j.molimm.2011.02.001.
Massi MN, Hidayah N, Handayani I, Iskandar IW, Djannah F, Angria N, Halik H. 2023. microRNA hsa-miR-425-5p and hsa-miR-4523 expressions as biomarkers of active pulmonary tuberculosis, latent tuberculosis infection, and lymph node tuberculosis. Noncoding RNA Res 8 (4): 527-533. DOI: 10.1016/j.ncrna.2023.07.001.
Muñoz L, Stagg RH, Abubakar I. 2015. Diagnosis and management of latent tuberculosis infection. Cold Spring Harb Perspect Med 5 (11): a017830. DOI: 10.1101/cshperspect.a017830.
Ndzi EN, Nkenfou CN, Pefura EWY, Mekue LCM, Guiedem E, Nguefeu CN, Ngoufack MN, Elong E, Yatchou LG, Ndjolo A, Kuiate J-R. 2019. Tuberculosis diagnosis: Algorithm that May discriminate latent from active tuberculosis. Heliyon 5 (10): e02559. DOI: 10.1016/j.heliyon.2019.e02559.
Peltier HJ, Latham GJ. 2008. Normalization of microRNA expression levels in quantitative RT-PCR assays: Identification of suitable reference RNA targets in normal and cancerous human solid tissues. RNA 14 (5): 844-852. DOI: 10.1261/rna.939908.
Penn-Nicholson A, Mbandi SK, Thompson E et al. 2020. RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response. Sci Rep 10 (1): 8629. DOI: 10.1038/s41598-020-65043-8.
Pierce S, Geanes ES, Bradley T. 2020. Targeting natural killer cells for improved immunity and control of the adaptive immune response. Front Cell Infect Microbiol 10: 231. DOI: 10.3389/fcimb.2020.00231.
Qureshi R, Sacan A. 2013. A novel method for the normalization of microRNA RT-PCR data. BMC Med Genomics 6 (Suppl 1): S14. DOI: 10.1186/1755-8794-6-S1-S14.
Ratti M, Lampis A, Ghidini M, Salati M, Mirchev MB, Valeri N, Hahne JC. 2020. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) as new tools for cancer therapy: First steps from bench to bedside. Target Oncol 15 (3): 261-278. DOI: 10.1007/s11523-020-00717-x.
Ruiz-Tagle C, Naves R, Balcells ME. 2020. Unraveling the role of micrornas in Mycobacterium tuberculosis infection and disease: Advances and pitfalls. Infect Immun 88: e00649-19. DOI: 10.1128/IAI.00649-19.
Sabir N, Hussain T, Shah SZA, Peramo A, Zhao D, Zhou X. 2018. miRNAs in tuberculosis: New avenues for diagnosis and host-directed therapy. Front Microbiol 9: 602. DOI: 10.3389/fmicb.2018.00602.
Shepelkova GS, Evstifeev VV, Tarasov RV, Ergeshova AE, Bagirov MA, Yeremeev VV. 2023. MicroRNAs as biomarkers of active pulmonary TB course. Microorganisms 11 (3): 626. DOI: 10.3390/microorganisms11030626.
Sinigaglia A, Peta E, Riccetti S, Venkateswaran S, Manganelli R, Barzon L. 2020. Tuberculosis-associated MicroRNAs: From pathogenesis to disease biomarkers. Cells 9 (10): 2160. DOI: 10.3390/cells9102160.
Sun X, Liu K, Zhao Y, Zhang T. 2022. High miRNA-378 expression has high diagnostic values for pulmonary tuberculosis and predicts adverse outcomes. BMC Mol Cell Biol 23 (1): 14. DOI: 10.1186/s12860-022-00413-w.
Susilawati TN, Larasati R. 2019. A recent update of the diagnostic methods for tuberculosis and their applicability in Indonesia: A narrative review. Med J Indones 28: 284-291. DOI: 10.13181/mji.v28i3.2589.
Veryaskina YA, Titov SE, Zhimulev IF. 2022. Reference genes for qPCR-based miRNA expression profiling in 14 human tissues. Med Princ Pract 31 (4): 322-332. DOI: 10.1159/000524283.
Wang C, Yang S, Sun G, Tang X, Lu S, Neyrolles O, Gao Q. 2011. Comparative mirna expression profiles in individuals with latent and active tuberculosis. PLoS One 6 (10): e25832. DOI: 10.1371/journal.pone.0025832.
WHO [World Health Organization]. 2021. Global Tuberculosis Report 2021. World Health Organization, Geneva.
Wikanningtyas TA, Hatta M, Massi MN, Pratiwi I, Fachri M, Santoso SS, Syarifuddin A, Dwiyanti R, Noviyanthi RA. 2018. Diagnosis of a spectrum of pulmonary tuberculosis at Islam Hospital Sukapura, Jakarta, Indonesia: A retrospective study of 317 cases. J Med Sci 18 (3): 143-148. DOI: 10.3923/jms.2018.143.148.
Yi Z, Fu Y, Ji R, Li R, Guan Z. 2012. Altered microRNA signatures in sputum of patients with active pulmonary tuberculosis. PLoS One 7 (8): e43184. DOI: 10.1371/journal.pone.0043184.
Zhou M, Yu G, Yang X, Zhu C, Zhang Z, Zhan X. 2016. Circulating microRNAs as biomarkers for the early diagnosis of childhood tuberculosis infection. Mol Med Rep 13 (6): 4620-4626. DOI: 10.3892/mmr.2016.5097.