miR-122: A New Target for Diagnosis and Treatment of Liver Diseases
Article Sidebar
Main Article Content
Abstract
miR-122 is a small single-stranded RNA molecule with approximately 20-22 nucleotides in length. It is well documented that miR-122 is a liver-specific miRNA that is expressed predominantly in liver cells and involved in a plenty of physiological processes of the liver function including the regulations of cholesterol level and fatty acid metabolism, liver cell differentiation and liver development, and suppression of hepatocarcinogenesis. miR-122 plays a crucial role in liver diseases, e.g., hepatitis B virus-associated hepatocellular carcinoma and human non-alcoholic steatohepatitis that are associated with reduced miR-122 expression. miR-122 is highly expressed in the adult liver, which can be detected in the circulation and serum. It also serves as a specific biomarker of some forms of liver pathogenesis: miR-122 is a sensitive marker for early detection of paracetamol-induced liver injury at 3 hours when there is neither significant morphological change nor elevation of alanine transaminase (ALT), aspartate transaminase (AST) or total bilirubin (TBIL) that could be detected. Thus, miR-122 is a promising biomarker for diagnosis of drug-induced liver injury, prognosis assessment as well as a drug target (i.e., miRNA-based therapeutic approaches) for treatment of viral hepatitis.
Article Details
References
Panyasai S. MicroRNA : Biosynthesis function and the important role in erythropoiesis. J Med Tech Phy Ther 2012; 24(3): 235-43.
O’Brien J, Hayder H, Zayed Y, et al. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol 2018; 9: 1-12.
MacFarlane LA, Murphy PR. MicroRNA: Biogenesis, function and role in cancer Curr Genomics 2010; 11: 537-61
Ha M, Kim NV. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 2014; 15: 509-24.
miRBase. miRBase: the microRNA database. 2018; Available at https://www.mirbase.org/index.shtml, accessed on September 20, 2021
Chang J, Patrick Provost P, Taylor JM. Resistance of human hepatitis delta virus RNAs to Dicer activity. J Virol 2003; 77(22): 11910–17.
Lagos-Quintana M, Rauhut R, Yalcin A, et al. Identification of tissue-specific micro RNAs from mouse. Curr Biol 2002; 12: 735–73.
Chang J, Nicolas E, Marks D, et al. miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol 2004; 1(2): 106-113.
Jopling CL, Yi M, Lancaster AM. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 2005; 2(309): 1577-81.
Girard M, Jacquemin E, Munnich A, et al. miR-122, a paradigm for the role of microRNAs in the liver. Hepatology 2008; 48(4): 648-56.
Janssen HLA, Reesink HW, Lawitz EJ, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med 2013; 368(18): 1685-94.
Agostini M, Knight RA. miR-34: from bench to bedside. Oncotarget 2014; 5(4): 872-81.
Cermelli S, Ruggieri A, Marrero JA, et al. Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty fiver disease. PLoS ONE 2011; 6(8): e23937.
Sharapova T, Devanarayan V, LeRoy B, et al. Evaluation of miR-122 as a serum biomarker for hepatotoxicity in investigative rat toxicology studies. Vet Pathol 2016; 53(1): 211-21.
Starkey Lewis PJ, Dear J, Platt V, et al. Circulating microRNAs as potential markers of human drug-induced liver injury. Hepatology 2011; 54(5): 1767-76.
van der Meer AJ, Farid WRR, Sonneveld MJ, et al. Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122. J Viral Hepat 2013; 20(3): 158-66.
Thakral S, Ghoshal K. miR-122 is a unique molecule with great potential in diagnosis, prognosis of liver disease, and therapy both as miRNA mimic and antimir. Curr Gene Ther 2015; 15(2): 142-50.
Deng XG, Qiu RL, Wu YH, et al. Overexpression of miR-122 promotes the hepatic differentiation and maturation of mouse ESCs through a miR-122/FoxA1/HNF4a-positive feedback loop. Liver Int 2014; 34(2): 281-95.
Xu H, He JH, Xiao ZD, et al. Liver-enriched transcription factors regulate microRNA-122 that targets CUTL1 during liver development. Hepatology 2010; 52(4): 1431-42.
Laudadio I, Manfroid I, Achouri Y, et al. A feedback loop between the liver-enriched transcription factor network and mir-122 controls hepatocyte differentiation. Gastroenterology 2012; 142(1): 119-29.
Coulouarn C, Factor CVM, Andersen JB, et al. Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene 2009; 28: 3526-36.
Esau C, Davis S, Murray SF, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 2006; 3(2): 87-98.
Elmén J, Lindow M, Schütz S, et al. LNA-mediated microRNA silencing in non-human primates. Nature 2008; 452: 896–99.
Krützfeldt J, Rajewsky N, Braich R, et al. Silencing of microRNAs in vivo with ‘antagomirs’. Nature 2005; 438: 685–89.
Gatfield D, Martelot GL, Vejnar CE, et al. Integration of microRNA miR-122 in hepatic circadian gene expression. Genes Dev 2009; 23: 1313-26.
Elmén J, Lindow M, Silahtaroglu A, et al. Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver. Nucleic Acids Res 2008; 36(4): 1153–62.
Moore KJ, Rayner KJ, Suárez Y, et al. microRNAs and cholesterol metabolism. Trends Endocrinol Metab 2010; 21(12): 699–706.
Norman KL, Sarnow P. Modulation of hepatitis C virus RNA abundance and the isoprenoid biosynthesis pathway by microRNA miR-122 involves distinct mechanisms. J Virol 2010; 84(1): 666–70.
Hsu SH, Wang B, Kota J, et al. Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver. J Clin Investig 2012; 122(8): 2871-83.
Tsai WC, Hsu SD, Hsu CS, et al. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J Clin Investig 2012; 122(8): 2884-97.
Bai S, Nasser MW, Wang B, et al. MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem 2009; 284(46): 32015-27.
Coulouarn C, Corlu A, Glaise D, et al. Hepatocyte-stellate cell cross-talk in the liver engenders a permissive inflammatory microenvironment that drives progression in hepatocellular carcinoma. Cancer Res 2012; 72(10): 2533-42.
Fornari F, Gramantieri L, Giovannini C, et al. MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res 2009; 69(14): 5761-67.
Nakao K, Miyaaki H, Ichikawa K. Antitumor function of microRNA-122 against hepatocellular carcinoma. J Gastroenterol 2014; 49(4): 589-93.
Nassirpour R, Mehta PP, Yin MJ. miR-122 regulates tumorigenesis in hepatocellular carcinoma by targeting AKT3. PLoS ONE 2013; 8(11): e79655.
Xu J, Zhu X, Wu L, et al. MicroRNA-122 suppresses cell proliferation and induces cell apoptosis in hepatocellular carcinoma by directly targeting Wnt/β-catenin pathway. Liver Int 2012; 32(5): 752-60.
Zeng C, Wang R, Li D, et al. A novel GSK-3 beta-C/EBP alpha-miR-122-insulin-like growth factor 1 receptor regulatory circuitry in human hepatocellular carcinoma. Hepatology 2010; 52(5): 1702-12.
Xu Y, Xia F, Ma L, et al. MicroRNA-122 sensitizes HCC cancer cells to adriamycin and vincristine through modulating expression of MDR and inducing cell cycle arrest. Cancer Lett 2011; 310(2): 160-69.
Spaniel C, Honda M, Selitsky SR, et al. microRNA-122 abundance in hepatocellular carcinoma and non-tumor liver tissue from Japanese patients with persistent HCV versus HBV infection. PLoS ONE 2013; 8(10): e76867.
Varnholt H, Drebber U, Schulze F, et al. MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma. Hepatology 2008; 47(4): 1223-32.
Baumert TF, Meredith L, Ni Y, et al. Entry of hepatitis B and C viruses-recent progress and future impact. Curr Opin Virol 2014; 4: 58-65.
Grimm D, Thimme R, Blum HE. HBV life cycle and novel drug targets. Hepatol Int 2011; 5(2): 644-53.
Lohmann V. Hepatitis C virus RNA replication. Curr Top Microbiol Immunol 2013; 369: 167-98.
Zeisel MB, Lupberger J, Fofana I. Host-targeting agents for prevention and treatment of chronic hepatitis C - perspectives and challenges. J Hepatol 2013; 58(2): 375-84.
Liu WH, Yeh SH, Chen PJ. Role of microRNAs in hepatitis B virus replication and pathogenesis. Biochim Biophys Acta 2011; 1809(11-12): 678-85.
Shrivastava S, Mukherjee A, Ray RB. Hepatitis C virus infection, microRNA and liver disease progression. World J Hepatol 2013; 5(9): 479-86.
Chen Y, Shen A, Rider PJ, et al. A liver-specific microRNA binds to a highly conserved RNA sequence of hepatitis B virus and negatively regulates viral gene expression and replication. FASEB J 2011; 25(12): 4511-21.
Murakami Y, Aly HH, Tajima A, et al. Regulation of the hepatitis C virus genome replication by miR-199a. J Hepatol 2009; 50: 453–60.
Zhang GL, Li YX, Zheng SQ, et al. Suppression of hepatitis B virus replication by microRNA-199a-3p and microRNA-210. Antiviral Res 2010; 8(2): 169-75.
Trépo C, Chan HYL, Lok A. Hepatitis B virus infection. Lancet 2014; 384(9959): 2053-63.
Fani M, Zandi M, Rezayi M, et al. The role of microRNAs in the viral infections. Curr Pharm Des 2018; 24(39): 4659-67.
Wang S, Qiu L, Yan X, 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.
Qiu L, Fan H, Jin W, et al. miR-122-induced down-regulation of HO-1 negatively affects miR-122-mediated suppression of HBV. Biochem Biophys Res Commun 2010; 398(4): 771-77.
Peng F, Xiao X, Jiang Y, et al. HBx down-regulated Gld2 plays a critical role in HBV-related dysregulation of miR-122. PLoS ONE 2014; 9(3): e92998.
Song K, Han C, Zhang J, et al. Epigenetic regulation of MicroRNA-122 by peroxisome proliferator activated receptor-gamma and hepatitis b virus X protein in hepatocellular carcinoma cells. Hepatology 2013; 58(5): 1681-92.
Fan CG, Wang CM, Tian C, et al. miR-122 inhibits viral replication and cell proliferation in hepatitis B virus-related hepatocellular carcinoma and targets NDRG3. Oncol Rep 2011; 26(5): 1281-86.
Li C, Wang Y, Wang S, et al. Hepatitis B virus mRNA-mediated miR-122 inhibition upregulates PTTG1-binding protein, which promotes hepatocellular carcinoma tumor growth and cell invasion. J Virol 2013; 87(4): 2193-205.
Wen W, Ding J, Sun W, et al. Cyclin G1-mediated epithelial-mesenchymal transition via phosphoinositide 3-kinase/Akt signaling facilitates liver cancer progression. Hepatology 2012; 55(6): 1787-98.
Lindenbach BD, Thiel HJ, Rice CM. Flaviviridae: the viruses and their replication. 5th ed. Philadelphia: Lippincott, Williams, and Wilki, 2007: 1101-52.
Henke JI, Goergen D, Zheng J, et al. microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J 2008; 27: 3300–10.
Jangra RK, Yi M, Lemon SM. Regulation of hepatitis C virus translation and infectious virus production by the microRNA miR-122. J Virol 2010; 84(13): 6615-25.
Goergen D, Niepmann M. Stimulation of Hepatitis C Virus RNA translation by microRNA-122 occurs under different conditions in vivo and in vitro. Virus Res 2012; 167(2): 343-52.
Chang J, Guo J-T, Jiang D, et al. Liver-specific microRNA miR-122 enhances the replication of hepatitis C virus in nonhepatic cells. J Virol 2008; 82: 8215–23.
Costa DD, Turek M, Felmlee DJ, et al. Reconstitution of the entire hepatitis C virus life cycle in nonhepatic cells. J Virol 2012; 86: 11919–25.
Fukuhara T, Kambara H, Shiokawa M, et al. Expression of microRNA miR-122 facilitates an efficient replication in nonhepatic cells upon infection with hepatitis C virus. J Virol 2012; 86(15): 7918-33.
Hueging K, Doepke M, Vieyres G, et al. Apolipoprotein E codetermines tissue tropism of hepatitis C virus and is crucial for viral cell-to-cell transmission by contributing to a postenvelopment step of assembly. J Virol 2014; 88: 1433–46.
Kambara H, Fukuhara T, Shiokawa M, et al. Establishment of a novel permissive cell line for the propagation of hepatitis C virus by expression of microRNA miR122. J Virol 2012; 86: 1382–93.
Hou W, Bukong TN, Kodys K, et al. Alcohol facilitates HCV RNA replication via up-regulation of miR-122 expression and inhibition of cyclin G1 in human hepatoma cells. Alcohol Clin Exp Res 2013; 37: 599–608.
Shan Y, Zheng J, Lambrecht RW, et al. Reciprocal effects of micro-RNA-122 on expression of heme oxygenase-1 and hepatitis C virus genes in human hepatocytes. Gastroenterology 2007; 133: 1166–74.
Estrabaud E, Lapalus M, Broët P, et al. Reduction of microRNA 122 expression in IFNL3 CT/TT carriers and during progression of fibrosis in patients with chronic hepatitis C. J Virol 2014; 88: 6394–402.
Kamo Y, Ichikawa T, Miyaaki H, et al. Significance of miRNA-122 in chronic hepatitis C patients with serotype 1 on interferon therapy. Hepatol Res 2015; 45: 88–96.
Sarasin-Filipowicz M, Krol J, Markiewicz I, et al. Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy. Nat Med 2009; 15: 31-33.
Su TH, Liu CH, Liu CJ, et al. Serum microRNA-122 level correlates with virologic responses to pegylated interferon therapy in chronic hepatitis C. Proc Natl Acad Sci U S A 2013; 110: 7844–49.
Köberle V, Waidmann O, Kronenberger B, et al. Serum microRNA-122 kinetics in patients with chronic hepatitis C virus infection during antiviral therapy. J Viral Hepat 2013; 20: 530-35.
Hildebrandt-Eriksen ES, Aarup V, Persson R, et al. A locked nucleic acid oligonucleotide targeting microRNA 122 is well-tolerated in cynomolgus monkeys. Nucleic Acid Ther 2012; 22: 152-61.
Janssen HLA, Reesink HW, Lawitz EJ, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med 2013; 368: 1685–94.
Chung RT, Baumert TF. Curing chronic hepatitis C – The arc of a medical triumph. N Engl J Med 2014; 370: 1576–78.
Haldipur B, Bhukya PL, Arankalle V. Positive regulation of hepatitis E virus replication by microRNA-122. J Virol 2018; 92: e01999-17.
Liu Y, Li P, Liu L, et al. The diagnostic role of miR-122 in drug-induced liver injury. Medicine (Baltimore) 2018; 97(49): e13478.
Kullak-Ublick GA, Andrade RJ, Merz M, et al. Drug-induced liver injury: recent advances in diagnosis and risk assessment. Gut 2017; 66: 1154–64.
Padda MS, Sanchez M, Akhtar AJ, et al. Drug-induced cholestasis. Hepatol 2011; 53: 1377–87.
Re 3rd VL, Haynes K, Forde KA, et al. Risk of acute liver failure in patients with drug-induced liver injury: evaluation of Hy’s law and a new prognostic model. Clin Gastroenterol Hepatol 2015; 13: 2360–68.
Hayashi PH, Rockey DC, Fontana RJ, et al. Death and liver transplantation within 2 years of onset of drug-induced liver injury. Hepatol 2017; 66: 1275–85.
Nathwani RA, Pais S, Reynolds TB, et al. Serum alanine aminotransferase in skeletal muscle diseases. Hepatol 2005; 41: 380–82.
Church RJ, Watkins PB. The transformation in biomarker detection and management of drug-induced liver injury. Liver Int 2017; 37(1582–90).
Bandiera S, Pfeffer S, Baumert TF. miR-122 – A key factor and therapeutic target in liver disease. Hepatology 2015; 62: 448–57.
