{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T23:28:01Z","timestamp":1793402881918,"version":"4.5.0"},"reference-count":99,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:00:00Z","timestamp":1731542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Pisa","award":["PRA2022_60"],"award-info":[{"award-number":["PRA2022_60"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a growing health concern worldwide, affecting more than 1 billion adults. It may progress to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and ultimately hepatocellular carcinoma (HCC). Emerging evidence has demonstrated the role in this transition of microRNAs (miRNAs), which regulate the expression of genes associated with lipid metabolism, inflammation, fibrosis, and cell proliferation. Specific miRNAs have been identified to exacerbate or mitigate fibrotic and carcinogenic processes in hepatic cells. The modulation of these miRNAs through synthetic mimics or inhibitors represents a promising therapeutic strategy. Preclinical models have demonstrated that miRNA-based therapies can attenuate liver inflammation, reduce fibrosis, and inhibit tumorigenesis, thus delaying or preventing the onset of HCC. However, challenges such as delivery mechanisms, off-target effects, and long-term safety remain to be addressed. This review, focusing on recently published preclinical and clinical studies, explores the pharmacological potential of miRNA-based interventions to prevent MASLD\/MASH and progression toward HCC.<\/jats:p>","DOI":"10.3390\/ijms252212229","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T08:06:32Z","timestamp":1731571592000},"page":"12229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Recent Advances in miRNA-Based Therapy for MASLD\/MASH and MASH-Associated HCC"],"prefix":"10.3390","volume":"25","author":[{"given":"Sara","family":"Carpi","sequence":"first","affiliation":[{"name":"Department of Health Sciences, University \u2018Magna Gr\u00e6cia\u2019 of Catanzaro, 88100 Catanzaro, Italy"},{"name":"NEST (National Enterprise for nanoScience and nanoTechnology), Istituto Nanoscienze-CNR and Scuola Normale Superiore, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7391-3087","authenticated-orcid":false,"given":"Simona","family":"Daniele","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline F\u00e1tima Martins","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2247-8227","authenticated-orcid":false,"given":"Daniela","family":"Gabbia","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/S0025-6196(24)00530-5","article-title":"Nonalcoholic Steatohepatitis: Mayo Clinic Experiences with a Hitherto Unnamed Disease","volume":"55","author":"Ludwig","year":"1980","journal-title":"Mayo Clin. Proc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1097\/HEP.0000000000000520","article-title":"A Multi-Society Delphi Consensus Statement on New Fatty Liver Disease Nomenclature","volume":"78","author":"Rinella","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.cmet.2024.03.011","article-title":"New and Emerging Treatments for Metabolic Dysfunction-Associated Steatohepatitis","volume":"36","author":"Tincopa","year":"2024","journal-title":"Cell Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.jhep.2024.04.036","article-title":"A Turning Point in Hepatology? EASL Reflects on the First Approved Drug for MASH","volume":"81","author":"Francque","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1136\/gutjnl-2018-318146","article-title":"miRNAs and NAFLD: From Pathophysiology to Therapy","volume":"68","author":"Gjorgjieva","year":"2019","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/35057062","article-title":"Initial Sequencing and Analysis of the Human Genome","volume":"409","author":"Lander","year":"2001","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/0092-8674(93)90529-Y","article-title":"The C. Elegans Heterochronic Gene Lin-4 Encodes Small RNAs with Antisense Complementarity to Lin-14","volume":"75","author":"Lee","year":"1993","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/nrg2504","article-title":"Small Silencing RNAs: An Expanding Universe","volume":"10","author":"Ghildiyal","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"R17","DOI":"10.1093\/hmg\/ddl046","article-title":"Non-Coding RNA","volume":"15","author":"Mattick","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nrm3838","article-title":"Regulation of microRNA Biogenesis","volume":"15","author":"Ha","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"D155","DOI":"10.1093\/nar\/gky1141","article-title":"miRBase: From microRNA Sequences to Function","volume":"47","author":"Kozomara","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mohr, R., \u00d6zdirik, B., Lambrecht, J., Demir, M., Eschrich, J., Geisler, L., Hellberg, T., Loosen, S.H., Luedde, T., and Tacke, F. (2021). From Liver Cirrhosis to Cancer: The Role of Micro-RNAs in Hepatocarcinogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031492"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41576-023-00662-1","article-title":"Non-Coding RNAs in Disease: From Mechanisms to Therapeutics","volume":"25","author":"Nemeth","year":"2024","journal-title":"Nat. Rev. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.cell.2010.02.020","article-title":"MicroRNAs: From Decay to Decoy","volume":"140","author":"Beitzinger","year":"2010","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"O\u2019Brien, J., Hayder, H., Zayed, Y., and Peng, C. (2018). Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00402"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/17474124.2024.2374472","article-title":"From NAFLD to MASLD: What Does It Mean?","volume":"18","author":"Chrysavgis","year":"2024","journal-title":"Exp. Rev. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1053\/j.gastro.2020.01.052","article-title":"Nonalcoholic Fatty Liver Disease 2020: The State of the Disease","volume":"158","author":"Cotter","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.tem.2024.02.007","article-title":"Current Status and Future Trends of the Global Burden of MASLD","volume":"35","author":"Miao","year":"2024","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gabbia, D., Cannella, L., and De Martin, S. (2021). The Role of Oxidative Stress in NAFLD\u2013NASH\u2013HCC Transition\u2014Focus on NADPH Oxidases. Biomedicines, 9.","DOI":"10.3390\/biomedicines9060687"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gabbia, D., and De Martin, S. (2023). Targeting the Adipose Tissue\u2013Liver\u2013Gut Microbiota Crosstalk to Cure MASLD. Biology, 12.","DOI":"10.3390\/biology12121471"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.2147\/DDDT.S315724","article-title":"Non-Alcoholic Steatohepatitis (NASH)\u2014A Review of a Crowded Clinical Landscape, Driven by a Complex Disease","volume":"15","author":"Fraile","year":"2021","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Longo, M., Paolini, E., Meroni, M., and Dongiovanni, P. (2021). Remodeling of Mitochondrial Plasticity: The Key Switch from NAFLD\/NASH to HCC. Int. J. Mol. Sci., 22.","DOI":"10.20944\/preprints202103.0714.v1"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global Burden of NAFLD and NASH: Trends, Predictions, Risk Factors and Prevention","volume":"15","author":"Younossi","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.cgh.2018.05.057","article-title":"Nonalcoholic Steatohepatitis Is the Fastest Growing Cause of Hepatocellular Carcinoma in Liver Transplant Candidates","volume":"17","author":"Younossi","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ramai, D., Tai, W., Rivera, M., Facciorusso, A., Tartaglia, N., Pacilli, M., Ambrosi, A., Cotsoglou, C., and Sacco, R. (2021). Natural Progression of Non-Alcoholic Steatohepatitis to Hepatocellular Carcinoma. Biomedicines, 9.","DOI":"10.3390\/biomedicines9020184"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/s41575-019-0145-7","article-title":"From NASH to HCC: Current Concepts and Future Challenges","volume":"16","author":"Anstee","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Castellana, M., Donghia, R., Lampignano, L., Castellana, F., Zupo, R., Sardone, R., Pergola, G.D., and Giannelli, G. (2021). Prevalence of the Absence of Cirrhosis in Subjects with NAFLD-Associated Hepatocellular Carcinoma. J. Clin. Med., 10.","DOI":"10.3390\/jcm10204638"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1016\/j.jhep.2011.10.027","article-title":"Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease: An Emerging Menace","volume":"56","author":"Baffy","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/ar.23954","article-title":"Role of MicroRNAs in the Development of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease","volume":"302","author":"Zhang","year":"2019","journal-title":"Anat. Rec."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ncrna.2023.10.010","article-title":"miRNA and lncRNA as Potential Tissue Biomarkers in Hepatocellular Carcinoma","volume":"9","author":"Mallela","year":"2024","journal-title":"Noncoding RNA Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sayed, G.I., Solyman, M., El Gedawy, G., Moemen, Y.S., Aboul-Ella, H., and Hassanien, A.E. (2024). Circulating miRNA\u2019s Biomarkers for Early Detection of Hepatocellular Carcinoma in Egyptian Patients Based on Machine Learning Algorithms. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-54795-2"},{"key":"ref_32","first-page":"3917","article-title":"Comprehensive Evaluation of microRNA as a Biomarker for the Diagnosis of Hepatocellular Carcinoma","volume":"28","author":"Malik","year":"2022","journal-title":"WJ Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.semcdb.2021.04.006","article-title":"Therapeutic Strategies for miRNA Delivery to Reduce Hepatocellular Carcinoma","volume":"124","author":"Roy","year":"2022","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"88517","DOI":"10.18632\/oncotarget.19774","article-title":"MicroRNA Deregulation in Nonalcoholic Steatohepatitis-Associated Liver Carcinogenesis","volume":"8","author":"Ortega","year":"2017","journal-title":"Oncotarget"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101581","DOI":"10.1016\/j.molmet.2022.101581","article-title":"MicroRNAs in Non-Alcoholic Fatty Liver Disease: Progress and Perspectives","volume":"65","author":"Hochreuter","year":"2022","journal-title":"Mol. Metabol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/jat.2960","article-title":"Circulating microRNA 122 in the Methionine and Choline-Deficient Mouse Model of Non-Alcoholic Steatohepatitis","volume":"34","author":"Clarke","year":"2014","journal-title":"J. Appl. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cmet.2006.01.005","article-title":"miR-122 Regulation of Lipid Metabolism Revealed by in Vivo Antisense Targeting","volume":"3","author":"Esau","year":"2006","journal-title":"Cell Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1053\/j.gastro.2017.08.013","article-title":"Metabolic Circuit Involving Free Fatty Acids, microRNA 122, and Triglyceride Synthesis in Liver and Muscle Tissues","volume":"153","author":"Chai","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.cca.2015.05.002","article-title":"Longitudinal Study of Circulating miR-122 in a Rat Model of Non-Alcoholic Fatty Liver Disease","volume":"446","author":"Yamada","year":"2015","journal-title":"Clin. Chim. Acta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1080\/13813455.2019.1640744","article-title":"The miR-122 Inhibition Alleviates Lipid Accumulation and Inflammation in NAFLD Cell Model","volume":"127","author":"Hu","year":"2021","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.jhep.2014.10.004","article-title":"miR-122\u2014A Key Factor and Therapeutic Target in Liver Disease","volume":"62","author":"Bandiera","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Liu, A.M., Xu, Z., Shek, F.H., Wong, K.-F., Lee, N.P., Poon, R.T., Chen, J., and Luk, J.M. (2014). miR-122 Targets Pyruvate Kinase M2 and Affects Metabolism of Hepatocellular Carcinoma. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086872"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.1172\/JCI63455","article-title":"MicroRNA-122 Plays a Critical Role in Liver Homeostasis and Hepatocarcinogenesis","volume":"122","author":"Tsai","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1089\/nat.2019.0820","article-title":"Metabolic Benefits of MicroRNA-22 Inhibition","volume":"30","author":"Thibonnier","year":"2020","journal-title":"Nucleic Acid Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e001478","DOI":"10.1136\/bmjdrc-2020-001478","article-title":"Metabolic and Energetic Benefits of microRNA-22 Inhibition","volume":"8","author":"Thibonnier","year":"2020","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Thibonnier, M., and Ghosh, S. (2023). Strategy for Pre-Clinical Development of Active Targeting MicroRNA Oligonucleotide Therapeutics for Unmet Medical Needs. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087126"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Panella, R., Petri, A., Desai, B.N., Fagoonee, S., Cotton, C.A., Nguyen, P.K., Lundin, E.M., Wagshal, A., Wang, D.-Z., and N\u00e4\u00e4r, A.M. (2023). MicroRNA-22 Is a Key Regulator of Lipid and Metabolic Homeostasis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612870"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"176453","DOI":"10.1016\/j.ejphar.2024.176453","article-title":"Tyrosol Attenuates NASH Features by Reprogramming the Hepatic Immune Milieu","volume":"969","author":"Gabbia","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1002\/2211-5463.13026","article-title":"MiR-22 Modulates the Expression of Lipogenesis-Related Genes and Promotes Hepatic Steatosis in Vitro","volume":"11","author":"Yang","year":"2021","journal-title":"FEBS Open Bio"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5593","DOI":"10.1158\/1078-0432.CCR-10-1734","article-title":"miR-22 Promotes HBV-Related Hepatocellular Carcinoma Development in Males","volume":"17","author":"Jiang","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1136\/gutjnl-2016-312869","article-title":"miRNA-132 Induces Hepatic Steatosis and Hyperlipidaemia by Synergistic Multitarget Suppression","volume":"67","author":"Hanin","year":"2018","journal-title":"Gut"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41575-020-00366-5","article-title":"Nonalcoholic Steatohepatitis: The Role of Peroxisome Proliferator-Activated Receptors","volume":"18","author":"Francque","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1056\/NEJMoa2036205","article-title":"A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH","volume":"385","author":"Francque","year":"2021","journal-title":"N. Eng. J. Med."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wu, J., Nagy, L.E., Liangpunsakul, S., and Wang, L. (2021). Non-Coding RNA Crosstalk with Nuclear Receptors in Liver Disease. Biochim. Biophys. Acta (BBA)-Mol. Basis Dis., 1867.","DOI":"10.1016\/j.bbadis.2021.166083"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/j.1440-1746.2009.05949.x","article-title":"Effect of miRNA-10b in Regulating Cellular Steatosis Level by Targeting PPAR-\u03b1 Expression, a Novel Mechanism for the Pathogenesis of NAFLD","volume":"25","author":"Zheng","year":"2010","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1053\/j.gastro.2020.12.062","article-title":"miR-10b-5p Rescues Diabetes and Gastrointestinal Dysmotility","volume":"160","author":"Singh","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1007\/s00432-015-1943-0","article-title":"Combination of Exosomes and Circulating microRNAs May Serve as a Promising Tumor Marker Complementary to Alpha-Fetoprotein for Early-Stage Hepatocellular Carcinoma Diagnosis in Rats","volume":"141","author":"Liu","year":"2015","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Zhu, Q., Gong, L., Wang, J., Tu, Q., Yao, L., Zhang, J.-R., Han, X.-J., Zhu, S.-J., Wang, S.-M., and Li, Y.-H. (2016). miR-10b Exerts Oncogenic Activity in Human Hepatocellular Carcinoma Cells by Targeting Expression of CUB and Sushi Multiple Domains 1 (CSMD1). BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2801-4"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nature10112","article-title":"MicroRNAs 103 and 107 Regulate Insulin Sensitivity","volume":"474","author":"Trajkovski","year":"2011","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/nm1557","article-title":"Targeted Disruption of AdipoR1 and AdipoR2 Causes Abrogation of Adiponectin Binding and Metabolic Actions","volume":"13","author":"Yamauchi","year":"2007","journal-title":"Nat. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/90984","article-title":"The Fat-Derived Hormone Adiponectin Reverses Insulin Resistance Associated with Both Lipoatrophy and Obesity","volume":"7","author":"Yamauchi","year":"2001","journal-title":"Nat. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"511","DOI":"10.3748\/wjg.v21.i2.511","article-title":"miRNA-103: Molecular Link between Insulin Resistance and Nonalcoholic Fatty Liver Disease","volume":"21","author":"Xu","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s41420-021-00536-7","article-title":"Exosomes Secreted by Palmitic Acid-Treated Hepatocytes Promote LX-2 Cell Activation by Transferring miRNA-107","volume":"7","author":"Wang","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"154375","DOI":"10.1016\/j.prp.2023.154375","article-title":"The Role of miRNAs in Liver Diseases: Potential Therapeutic and Clinical Applications","volume":"243","author":"Doghish","year":"2023","journal-title":"Pathol.-Res. Pract."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1080\/15476286.2018.1445959","article-title":"Anti-miRNA Oligonucleotides: A Comprehensive Guide for Design","volume":"15","author":"Lima","year":"2018","journal-title":"RNA Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"102184","DOI":"10.1016\/j.omtn.2024.102184","article-title":"Oligonucleotide Therapies for Nonalcoholic Steatohepatitis","volume":"35","author":"Li","year":"2024","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.trecan.2017.12.008","article-title":"MicroRNA-Based Drugs for Brain Tumors","volume":"4","author":"Anthiya","year":"2018","journal-title":"Trends Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Panella, R., Zanderigo, F., Morandini, F., Federico, D., Vicentini, E., Andreetta, F., Toniolo, A., and Kauppinen, S. (2023). Assessment of Immunostimulatory Responses to the antimiR-22 Oligonucleotide Compound RES-010 in Human Peripheral Blood Mononuclear Cells. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1125654"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e160","DOI":"10.1016\/S0618-8278(19)30284-1","article-title":"LBP-40-Development of Oligonucleotide-Based miR-132 Antagonists for the Treatment of NASH","volume":"70","author":"Papazyan","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s00125-014-3434-2","article-title":"Glucose Tolerance Is Associated with Differential Expression of microRNAs in Skeletal Muscle: Results from Studies of Twins with and without Type 2 Diabetes","volume":"58","author":"Scheele","year":"2015","journal-title":"Diabetologia"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12263-019-0630-1","article-title":"High-Throughput Sequencing of Small RNAs and Analysis of Differentially Expressed microRNAs Associated with High-Fat Diet-Induced Hepatic Insulin Resistance in Mice","volume":"14","author":"Zhao","year":"2019","journal-title":"Genes Nutr."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"613","DOI":"10.4254\/wjh.v6.i8.613","article-title":"Circulating microRNAs in Patients with Non-Alcoholic Fatty Liver Disease","volume":"6","author":"Celikbilek","year":"2014","journal-title":"World J. Hepatol."},{"key":"ref_73","unstructured":"RosVivo Therapeutics, Inc. (2024, October 02). Signed a Material Transfer Agreement (MTA) for First-in-Class Diabetes Treatment with Eli Lilly and Company. Available online: https:\/\/www.prnewswire.com\/news-releases\/rosvivo-therapeutics-inc-signed-a-material-transfer-agreement-mta-for-first-in-class-diabetes-treatment-with-eli-lilly-and-company-301487234.html."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"498232","DOI":"10.1155\/2012\/498232","article-title":"MicroRNA Signature in Alcoholic Liver Disease","volume":"2012","author":"Bala","year":"2012","journal-title":"Int. J. Hepatol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Riera, M., Conde, I., Tolosa, L., Zaragoza, \u00c1., Castell, J.V., G\u00f3mez-Lech\u00f3n, M.J., and Jover, R. (2017). New microRNA Biomarkers for Drug-Induced Steatosis and Their Potential to Predict the Contribution of Drugs to Non-Alcoholic Fatty Liver Disease. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00003"},{"key":"ref_76","unstructured":"(2024, October 02). Resalis Therapeutics Raises \u20ac10 Million Series A to Complete First Clinical Trial for RES-010 in Obesity. Available online: https:\/\/www.biospace.com\/resalis-therapeutics-raises-10-million-series-a-to-complete-first-clinical-trial-for-res-010-in-obesity."},{"key":"ref_77","unstructured":"(2024, October 02). Pipeline\u2014Resalis Therapeutics. Available online: https:\/\/www.resalistherapeutics.com\/science\/pipeline\/."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1194\/jlr.M800509-JLR200","article-title":"Differential Expression of microRNAs in Mouse Liver under Aberrant Energy Metabolic Status[S]","volume":"50","author":"Li","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/s41573-021-00219-z","article-title":"Noncoding RNA Therapeutics\u2014Challenges and Potential Solutions","volume":"20","author":"Winkle","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1080\/13543784.2020.1839888","article-title":"The Nonalcoholic Steatohepatitis (NASH) Drug Development Graveyard: Established Hurdles and Planning for Future Success","volume":"29","author":"Drenth","year":"2020","journal-title":"Exp. Opin. Investig. Drugs"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nbt.3765","article-title":"The Chemical Evolution of Oligonucleotide Therapies of Clinical Utility","volume":"35","author":"Khvorova","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"339","DOI":"10.4155\/fmc.11.2","article-title":"Antisense Drug Discovery and Development","volume":"3","author":"Yamamoto","year":"2011","journal-title":"Future Med. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/nature13975","article-title":"Towards a Therapy for Angelman Syndrome by Targeting a Long Non-Coding RNA","volume":"518","author":"Meng","year":"2015","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"143","DOI":"10.2174\/1874467214666210420113427","article-title":"siRNAs and Viruses: The Good, the Bad and the Way Forward","volume":"15","author":"Soobramoney","year":"2021","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.2174\/0929867325666181008142831","article-title":"Aptamer-Based Targeted Drug Delivery Systems: Current Potential and Challenges","volume":"27","author":"He","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Makowska, M., Smolarz, B., and Romanowicz, H. (2023). microRNAs (miRNAs) in Glioblastoma Multiforme (GBM)\u2014Recent Literature Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043521"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1016\/j.ymthe.2020.06.015","article-title":"Delivery of Oligonucleotides to the Liver with GalNAc: From Research to Registered Therapeutic Drug","volume":"28","author":"Debacker","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_88","first-page":"385","article-title":"MicroRNA and Liver Cancer","volume":"3","author":"Onishi","year":"2020","journal-title":"Cancer Drug Resist."},{"key":"ref_89","unstructured":"Misra, A. (2011). 7\u2014Antisense Oligonucleotides and RNA Interference. Challenges in Delivery of Therapeutic Genomics and Proteomics, Elsevier."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1158\/1535-7163.MCT-14-0209","article-title":"Systemic Delivery of a miR34a Mimic as a Potential Therapeutic for Liver Cancer","volume":"13","author":"Daige","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s10637-016-0407-y","article-title":"Phase I Study of MRX34, a Liposomal miR-34a Mimic, Administered Twice Weekly in Patients with Advanced Solid Tumors","volume":"35","author":"Beg","year":"2017","journal-title":"Investig. New Drugs"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.jconrel.2012.09.009","article-title":"A pH-Sensitive Cationic Lipid Facilitates the Delivery of Liposomal siRNA and Gene Silencing Activity in Vitro and in Vivo","volume":"163","author":"Sato","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1078\/0171-9335-00363","article-title":"PEGylation Significantly Affects Cellular Uptake and Intracellular Trafficking of Non-Viral Gene Delivery Particles","volume":"83","author":"Mishra","year":"2004","journal-title":"Eur. J. Cell Biol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Baldari, S., Di Rocco, G., Magenta, A., Picozza, M., and Toietta, G. (2019). Extracellular Vesicles\u2013Encapsulated MicroRNA-125b Produced in Genetically Modified Mesenchymal Stromal Cells Inhibits Hepatocellular Carcinoma Cell Proliferation. Cells, 8.","DOI":"10.3390\/cells8121560"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jconrel.2016.09.016","article-title":"Good Things Come in Small Packages: Overcoming Challenges to Harness Extracellular Vesicles for Therapeutic Delivery","volume":"241","author":"Ingato","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.omtm.2019.01.001","article-title":"Improved Loading of Plasma-Derived Extracellular Vesicles to Encapsulate Antitumor miRNAs","volume":"13","author":"Pomatto","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.addr.2014.10.031","article-title":"Recent Progress in microRNA Delivery for Cancer Therapy by Non-Viral Synthetic Vectors","volume":"81","author":"Wang","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.4155\/fmc.14.116","article-title":"miRNA-Based Therapies: Strategies and Delivery Platforms for Oligonucleotide and Non-Oligonucleotide Agents","volume":"6","author":"Baumann","year":"2014","journal-title":"Future Med. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4470","DOI":"10.1158\/0008-5472.CAN-15-2949","article-title":"Eradication of Acute Myeloid Leukemia with FLT3 Ligand-Targeted miR-150 Nanoparticles","volume":"76","author":"Jiang","year":"2016","journal-title":"Cancer Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/22\/12229\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:32:15Z","timestamp":1760113935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/22\/12229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,14]]},"references-count":99,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ijms252212229"],"URL":"https:\/\/doi.org\/10.3390\/ijms252212229","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,14]]}}}