MICRO-RNA AS POTENTIAL NON-INVASIVE MARKERS OF PATHOLOGICAL CONDITIONS OF THE LIVER
Abstract
The state of the cell (and the organism as a whole) is determined not only by the genotype, but by the ratio of turned on and off genes as well. Epigenetic regulation of gene expression plays a key role in the control of many cellular processes. Being important molecules of such regulation microRNAs are involved in post-transcriptional turning about half of human genes off. Abnormal expression of microRNAs, leading to changes in their concentration, can contribute to the development of many pathophysiological processes, diseases as well as cancer, and therefore microRNAs can be regarded as biomarkers for identifying various types of diseases. This mini-review presents the biogenesis, subcellular and exosomal localization of microRNAs and the mechanisms by which they regulate transcription and cellular homeostasis.
References
Huang DQ, Terrault NA, Tacke F, Gluud LL, Arrese M, Bugianesi E, Loomba R. Global epidemiology of cirrhosis – aetiology, trends and predictions. Nat Rev Gastroenterol Hepatol. 2023;20(6):388-398. https://doi.org/10.1038/s41575-023-00759-2.
Newman LA, Muller K, Rowland A. Circulating cell-specific extracellular vesicles as biomarkers for the diagnosis and monitoring of chronic liver diseases. Cell. Mol. Life Sci. 2022;79(5):232. https://doi.org/10.1007/s00018-022-04256-8.
Gosalia D, Ratziu V, Stanicic F, Vukicevic D, Zah V, Gunn N, Halegoua-DeMarzio D, Tran T. Accuracy of Noninvasive Diagnostic Tests for the Detection of Significant and Advanced Fibrosis Stages in Nonalcoholic Fatty Liver Disease: A Systematic Literature Review of the US Studies. Diagnostics. 2022;12(11):2608. https://doi.org/10.3390/diagnostics12112608.
Mohr R, Özdirik B, Lambrecht J, Demir M, Eschrich J, Geisler L, Hellberg T, Loosen SH, Luedde T, Tacke F, Hammerich L, Roderburg C. From Liver Cirrhosis to Cancer: The Role of Micro-RNAs in Hepatocarcinogenesis. Int. J. Mol. Sci. 2021;22(3):1492. https://doi.org/10.3390/ijms22031492.
Makarova JuA. Skolko u nas genov. Himija i zhizn. 2019;4:18-22. (Russian).
Nguyen TPN, Kumar M, Fedele E, Bonanno G, Bonifacino T. MicroRNA Alteration, Application as Biomarkers, and Therapeutic Approaches in Neurodegenerative Diseases. Int J Mol Sci. 2022;23(9):4718. https://doi.org/10.3390/ijms23094718.
Hombach S, Kretz M. Non-coding RNAs: Classification, Biology and Functioning. Adv Exp Med Biol. 2016;937:3-17. https://doi.org/10.1007/978-3-319-42059-2_1.
Yang SC, Alalaiwe A, Lin ZC, Lin YC, Aljuffali IA, Fang JY. Anti-Inflammatory microRNAs for Treating Inflammatory Skin Diseases. Biomolecules. 2022;12(8):1072. https://doi.org/10.3390/biom12081072.
Annese T, Tamma R, De Giorgis M, Ribatti D. MicroRNAs Biogenesis, Functions and Role in Tumor Angiogenesis. Front. Oncol. 2020;10:581007. https://doi.org/10.3389/fonc.2020.581007.
Liu J, Zhou F, Guan Y, Meng F, Zhao Z, Su Q, Bao W, Wang X, Zhao J, Huo Z, Zhang L, Zhou S, Chen Y, Wang X. The Biogenesis of miRNAs and Their Role in the Development of Amyotrophic Lateral Sclerosis. Cells. 2022;11(3):572. https://doi.org/10.3390/cells11030572.
Gurtner A, Falcone E, Garibaldi F, Piaggio G. Dysregulation of microRNA biogenesis in cancer: the impact of mutant p53 on Drosha complex activity. J Exp Clin Canc Res. 2016;35:45. https://doi.org/10.1186/s13046-016-0319-x.
Makarova YuA, Shkurnikov MYu, Wicklein D, Lange T, Samatov TR, Turchinovich AA, Tonevitsky AG. Intracellular and extracellular microRNA: an update on localization and biological role. Prog. Histochem. Cytochem. 2016;51(3-4):33-49. https://doi.org/10.1016/j.proghi.2016.06.001. https://elibrary.ru/xcofjl.
Semina EV, Rysenkova KD, Troyanovskiy KE, Shmakova AA, Rubina KA. MikroRNK v rake: ot reguljacii jekspressii genov do pereprogrammirovanija metastaticheskoj nishi [Мicrorna in oncology: from mechanisms of gene expression regulation to reprogramming of the metastatic niche]. Biohimija [Biochemistry]. 2021;86(5):672-688. https://doi.org/10.31857/S0320972521050055. https://elibrary.ru/waajqt. (Russian).
Catalanotto C, Cogoni C, Zardo G. Catalanotto, C. MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions. Int. J. Mol. Sci. 2016;17(10):1712. https://doi.org/10.3390/ijms17101712.
Jie M, Feng T, Huang W, Zhang M, Feng Y, Jiang H, Wen Z. Subcellular Localization of miRNAs and Implications in Cellular Homeostasis. Genes (Basel). 2021;12(6):856. https://doi.org/10.3390/genes12060856.
Szabo G, Bala S. MicroRNAs in liver disease. Nat Rev Gastroenterol Hepatol. 2013;10(9):542-52. https://doi.org/10.1038/nrgastro.2013.87.
Rodrigues SC, Cardoso RMS, Duarte FV. Mitochondrial microRNAs: A Putative Role in Tissue Regeneration. Biology. 2020;9(12):486. https://doi.org/10.3390/biology9120486.
Gao P, Yan Z, Zhu Z. Mitochondria-associated endoplasmic reticulum membranes in cardiovascular diseases. Front. Cell Dev. Biol. 2020;8:604240. https://doi.org/10.3389/FCELL.2020.604240.
Wang WX, Prajapati P, Nelson PT, Springer JE. The mitochondria-associated ER membranes are novel subcellular locations enriched for inflammatory-responsive MicroRNAs. Mol. Neurobiol. 2020;57(7):2996-3013. https://doi.org/10.1007/s12035-020-01937-y.
Duroux-Richard I, Apparailly F, Khoury M. Mitochondrial MicroRNAs Contribute to Macrophage Immune Functions Including Differentiation, Polarization, and Activation. Front. Physiol. 2021;12:738140. https://doi.org/10.3389/fphys.2021.738140.
Duarte FV, Palmeira CM, Rolo AP. The Emerging Role of MitomiRs in the Pathophysiology of Human Disease. Adv Exp Med Biol. 2015;888:123-54. https://doi.org/10.1007/978-3-319-22671-2_8.
Kuthethur R, Shukla V, Mallya S, Adiga D, Kabekkodu SP, Ramachandra L, Saxena PUP, Satyamoorthy K, Chakrabarty S. Expression analysis and function of mitochondrial genome-encoded microRNAs. J Cell Sci. 2022;135(8):jcs258937. https://doi.org/10.1242/jcs.258937.
Bian Z, Li LM, Tang R, Hou DX, Chen X, Zhang CY, Zen K. Identification of mouse liver mitochondria-associated miRNAs and their potential biological functions. Cell Res. 2010;20(9):1076-1078. https://doi.org/10.1038/cr.2010.119.
Jiao Y, Xu P, Shi H, Chen D, Shi H. Advances on liver cell-derived exosomes in liver diseases. J Cell Mol Med. 2021;25(1):15-26. https://doi.org/10.1111/jcmm.16123.
Hwang S, Yang YM. Exosomal microRNAs as diagnostic and therapeutic biomarkers in non-malignant liver diseases. Arch Pharm Res. 2021;44(6):574-587. https://doi.org/10.1007/s12272-021-01338-2.
Hirsova P, Ibrahim SH, Verma VK, Morton LA, Shah VH, LaRusso NF, Gores GJ, Malhi H. Extracellular vesicles in liver pathobiology: Small particles with big impact. Hepatology. 2016;64(6):2219-33. https://doi.org/10.1002/hep.28814.
Ye Q, Zhou Y, Zhao C, Xu L, Ping J. Salidroside inhibits CCl4-induced liver fibrosis in mice by reducing activation and migration of HSC induced by liver sinusoidal endothelial cell-derived exosomal SphK1. Front Pharmacol. 2021;12:677810. https://doi.org/10.3389/fphar.2021.677810.
Shen M, Shen Y, Fan X, Men R, Ye T, Yang L. Roles of Macrophages and Exosomes in Liver Diseases. Front Med (Lausanne). 2020;7:583691. https://doi.org/10.3389/fmed.2020.583691.
Banizs AB, Huang T, Nakamoto RK, Shi W, He J. Endocytosis pathways of endothelial cell derived exosomes. Mol Pharm. 2018;15(12):5585‐5590. https://doi.org/10.1021/acs.molpharmaceut.8b00765.
Wang C, Liu J, Yan Y, Tan Y. Role of Exosomes in Chronic Liver Disease Development and Their Potential Clinical Applications. J Immunol Res. 2022;6:1695802. https://doi.org/10.1155/2022/1695802.
Jiao Y, Xu P, Shi H, Chen D, Shi H. Advances on liver cell-derived exosomes in liver diseases. J Cell Mol Med. 2021;25(1):15-26. https://doi.org/10.1111/jcmm.16123.
Hessvik NP, Llorente A. Current knowledge on exosome biogenesis and release. Cell Mol Life Sci. 2018;75(2):193-208. https://doi.org/10.1007/s00018-017-2595-9.
Tamasi V, Németh K, Csala M. Role of Extracellular Vesicles in Liver Diseases. Csala Life (Basel). 2023;13(5):1117. https://doi.org/10.3390/life13051117.
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