Role of MicroRNAs in the Development of Chronic Liver Disease in Hepatitis Virus-Infected Egyptian Population
DOI:
https://doi.org/10.3889/oamjms.2022.10902Keywords:
Chronic liver disease, Hepatitis C Virus, Hepatocellular carcinoma, MicroRNAsAbstract
Background: The identification of miRNAs that play a role in the regulation of the viral life cycle and its related liver illness opens the door to the development of diagnostic biomarkers that can categorize patients at higher risk for developing end-stage liver disease. This study was designed to investigate the role of miRNAs in the development of viral hepatitis-induced chronic liver disease (CLD) in the Egyptian population, as well as their potential as possible diagnostic biomarkers for chronic hepatitis virus infection.
Methodology: The study involved 100 CLD patients; 55 cases of hepatitis C virus (HCV) and 45 cases of non-viral hepatitis, in addition to 40 healthy controls. The expression of five miRNAs (miR‐30, miR‐122, miR‐296, miR‐351, and miR‐431) was assessed using real-time PCR.
Results: Serum levels of miR‐30, miR‐122, miR‐296, miR‐351, and miR‐431 were significantly higher in all patients than the control group (p<0.01). Also, they were significantly greater in viral hepatitis cases compared to the non-viral hepatitis group (p<0.01). The sensitivities and specificities of miR-122a, miR‐30, miR‐296, miR‐351, and miR‐431 were (85.71%, 83.33%), (82.35%, 83.33%), (85.71%, 69.44%), (88.64%, 75.76%), and (87.80%, 65.79%), respectively.
Conclusions: miR‐30, miR‐122, miR‐296, miR‐351, and miR‐431 play key roles in the development of CLD as a consequence of viral infection. So, they have the potential to be targeted for the early detection of chronic hepatitis virus infection and allow for exploring a new frontier in the discovery of innovative therapeutics to combat chronic viral infection and its serious life-threatening complications including liver cancer.
Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Xiao J, Wang F, Wong NK, He J, Zhang R, Sun R, et al. Global liver disease burdens and research trends: Analysis from a Chinese perspective. J Hepatol. 2019;71(1):212-21. https://doi.org/10.1016/j.jhep.2019.03.004 PMid:30871980 DOI: https://doi.org/10.1016/j.jhep.2019.03.004
Alqahtani SA, Colombo M. Viral hepatitis as a risk factor for the development of hepatocellular carcinoma. Hepatoma Res. 2020;6:58. https://doi.org/10.20517/2394-5079.2020.49 DOI: https://doi.org/10.20517/2394-5079.2020.49
Sartorius K, An P, Winkler C, Chuturgoon A, Li X, Makarova J, et al. The epigenetic modulation of cancer and immune pathways in hepatitis B virus-associated hepatocellular carcinoma: The influence of HBx and miRNA dysregulation. Front Immunol. 2021;12:661204. https://doi.org/10.3389/fimmu.2021.661204 PMid:33995383 DOI: https://doi.org/10.3389/fimmu.2021.661204
Condrat CE, Thompson DC, Barbu MG, Bugnar OL, Boboc A, Cretoiu D, et al. miRNAs as biomarkers in disease: Latest findings regarding their role in diagnosis and prognosis. Cells. 2020;9(2):276. https://doi.org/10.3390/cells9020276 PMid:31979244 DOI: https://doi.org/10.3390/cells9020276
Zhu H, Geng Y, He Q, Li M. MiRNAs regulate immune response and signaling during hepatitis C virus infection. Eur J Med Res. 2018;23(1):19. https://doi.org/10.1186/s40001-018-0317-x PMid:29669594 DOI: https://doi.org/10.1186/s40001-018-0317-x
Chuaypen N, Limothai U, Kunadirek P, Kaewsapsak P, Kueanjinda P, Srisawat N, et al. Identification and validation of circulating miRNAs as potential new biomarkers for severe liver disease in patients with leptospirosis. PLoS One. 2021;16(9):e0257805. https://doi.org/10.1371/journal.pone.0257805 PMid:34570814 DOI: https://doi.org/10.1371/journal.pone.0257805
Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV, et al. Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature. 2007;449(7164):919-22. https://doi.org/10.1038/nature06205 PMid:17943132 DOI: https://doi.org/10.1038/nature06205
Liu X, Wang T, Wakita T, Yang W. Systematic identification of microRNA and messenger RNA profiles in hepatitis C virus-infected human hepatoma cells. Virology. 2010;398(1):57-67. https://doi.org/10.1016/j.virol.2009.11.036 PMid:20006370 DOI: https://doi.org/10.1016/j.virol.2009.11.036
Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101-8. https://doi.org/10.1038/nprot.2008.73 PMid:18546601 DOI: https://doi.org/10.1038/nprot.2008.73
Okasha H, Hassan M, Aboushousha T, Samir S. Effect of interferon-beta (IFN-β) on tumor suppressor and apoptotic markers in hepatocellular carcinoma cell line. Int J Res Pharm Sci. 2019;10(4):2936-43. https://doi.org/10.26452/ijrps.v10i4.1574 DOI: https://doi.org/10.26452/ijrps.v10i4.1574
Fabrellas N, Carol M, Palacio E, Aban M, Lanzillotti T, Nicolao G, et al. Nursing care of patients with cirrhosis: The liverhope nursing project. Hepatology. 2020;71(3):1106-16. https://doi.org/10.1002/hep.31117S PMid:31944340 DOI: https://doi.org/10.1002/hep.31117
Cox AL, El-Sayed MH, Kao JH, Lazarus JV, Lemoine M, Lok AS, et al. Progress towards elimination goals for viral hepatitis. Nat Rev Gastroenterol Hepatol. 2020;17(9):533-42. https://doi.org/10.1038/s41575-020-0332-6 PMid:32704164 DOI: https://doi.org/10.1038/s41575-020-0332-6
Khalifa RH, Labib DA, Kamel MA, Shahin RM, Bahgat DM, Riad NM, et al. Role of ApoB-516C/T promoter gene polymorphism in the risk of hepatitis C virus infection in Egyptian patients and in gender susceptibility. J Med Virol. 2017;89(9):1584-9. https://doi.org/10.1002/jmv.24815 PMid:28370191 DOI: https://doi.org/10.1002/jmv.24815
Crouchet E, Wrensch F, Schuster C, Zeisel MB, Baumert TF. Host-targeting therapies for hepatitis C virus infection: Current developments and future applications. Therap Adv Gastroenterol. 2018;11:1756284818759483. https://doi.org/10.1177/1756284818759483 PMid:29619090 DOI: https://doi.org/10.1177/1756284818759483
Schult P, Roth H, Adams RL, Mas C, Imbert L, Orlik C, et al. microRNA-122 amplifies hepatitis C virus translation by shaping the structure of the internal ribosomal entry site. Nat Commun. 2018;9(1):2613. https://doi.org/10.1038/s41467-018-05053-3 DOI: https://doi.org/10.1038/s41467-018-05053-3
Jopling CL. Targeting microRNA-122 to treat hepatitis C virus infection. Viruses. 2010;2(7):1382-93. https://doi.org/10.3390/v2071382 PMid:21994685 DOI: https://doi.org/10.3390/v2071382
Van Der Ree MH, Van Der Meer AJ, Van Nuenen AC, De Bruijne J, Ottosen S, Janssen HL, et al. Miravirsen dosing in chronic hepatitis C patients results in decreased microRNA-122 levels without affecting other microRNAs in plasma. Aliment Pharmacol Ther. 2016;43(1):102-13. https://doi.org/10.1111/apt.13432 PMid:26503793 DOI: https://doi.org/10.1111/apt.13432
Wang S, Qiu L, Yan X, Jin W, Wang Y, Chen L, et al. Loss of microRNA 122 expression in patients with hepatitis B enhances hepatitis B virus replication through cyclin G(1)-modulated P53 activity. Hepatology. 2012;55(3):730-41. https://doi.org/10.1002/hep.24809 PMid:22105316 DOI: https://doi.org/10.1002/hep.24809
Bandiera S, Pfeffer S, Baumert TF, Zeisel MB. miR-122--a key factor and therapeutic target in liver disease. J Hepatol. 2015;62(2):448-57. https://doi.org/10.1016/j.jhep.2014.10.004 PMid:25308172 DOI: https://doi.org/10.1016/j.jhep.2014.10.004
Hao J, Jin W, Li X, Wang S, Zhang X, Fan H, et al. Inhibition of alpha interferon (IFN-α)-induced microRNA-122 negatively affects the anti-hepatitis B virus efficiency of IFN-α. J Virol. 2013;87(1):137-47. https://doi.org/10.1128/JVI.01710-12 PMid:23055569 DOI: https://doi.org/10.1128/JVI.01710-12
Downloads
Published
How to Cite
License
Copyright (c) 2022 Marwa Hassan, Eman El-Ahwany, Mohamed Elzallat, Ali Abdel Rahim, Hoda Abu-Taleb, Yosry Abdelrahman, Moataz Hassanein (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
http://creativecommons.org/licenses/by-nc/4.0
Funding data
-
Theodor Bilharz Research Institute
Grant numbers Project No: 92 Diagnosis