Non-coding RNAs in alcohol-associated liver disease

Ge Zeng; Hui Gao; Yanchao Jiang; Nazmul Huda; Themis Thoudam; Zhihong Yang; Jing Ma; Jian Sun; Suthat Liangpunsakul

doi:10.1016/j.livres.2025.04.007

Liver Research ›› 2025, Vol. 9 ›› Issue (2) :81 -93. DOI: 10.1016/j.livres.2025.04.007

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Non-coding RNAs in alcohol-associated liver disease

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Abstract

Non-coding RNAs (ncRNAs), encompassing microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as critical regulators of gene expression and cellular function. In alcohol-associated liver disease (ALD), chronic alcohol consumption disrupts the expression and function of ncRNAs in the liver and circulation, contributing to the disease's pathogenesis and progression. Dysregulated ncRNAs influence key pathways involved in hepatocyte injury, lipid metabolism, inflammation, and hepatic stellate cell (HSC) activation, thereby exacerbating steatosis, inflammation, and fibrosis. Furthermore, extracellular vesicles play a pivotal role in mediating ncRNA-driven intercellular communication, amplifying liver damage and fibrosis. This review provides a comprehensive overview of the multifaceted roles of ncRNAs in ALD, with a focus on their mechanistic contributions to disease development and progression. Additionally, we discuss the potential of ncRNAs as diagnostic biomarkers and therapeutic targets, emphasizing their translational relevance in addressing the burden of ALD.

Keywords

Alcohol-associated liver disease (ALD) / Non-coding RNAs (ncRNAs) / MicroRNAs (miRNAs) / Circular RNAs (circRNAs) / Long non-coding RNAs (lncRNAs) / Biomarkers / Therapeutic targets

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Ge Zeng, Hui Gao, Yanchao Jiang, Nazmul Huda, Themis Thoudam, Zhihong Yang, Jing Ma, Jian Sun, Suthat Liangpunsakul. Non-coding RNAs in alcohol-associated liver disease. Liver Research, 2025, 9(2): 81-93 DOI:10.1016/j.livres.2025.04.007

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Author’s contributions

Ge Zeng: Writing e review & editing, Writing e original draft. Hui Gao: Writing e review & editing, Writing e original draft. Yanchao Jiang: Writing e review & editing. Nazmul Huda: Writing e review & editing. Themis Thoudam: Writing e review & editing. Zhihong Yang: Writing e review & editing. Jing Ma: Writing e review & editing. Jian Sun: Conceptualization, Supervision, Writing e review & editing. Suthat Liangpunsakul: Conceptualization, Supervision, Writing e review & editing.

Declaration of competing interest

None of the authors have any conflicts of interest with this work.

Acknowledgements

This work was supported by the National Key Research and Development Program of China (No.2022YFC2304800 to Ge Zeng); NIH K99AA031067, the CSCTR Early Career Development Award, and Indiana Clinical and Translational Sciences Institute grant UM1TR004402 (in part to Jing Ma); the National Institutes of Health (NIH R01AA030993 to Zhihong Yang); the American Liver Foun-dation Postdoctoral Award (in part to Themis Thoudam); and NIH grant R01AA030312, Department of Veterans Affairs Merit Awards 1I01CX000361 and I01BX006202, and the Indiana University School of Medicine Dean's Scholar Award (in part to Suthat Liangpunsakul).

References

Publishing order | Descend order by publishing year | Descend order by cited within

[1]	Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12: 861-874. https://doi.org/10.1038/nrg3074.

[2]	Boon RA, Jaé N, Holdt L, Dimmeler S. Long noncoding RNAs: from clinical genetics to therapeutic targets? J Am Coll Cardiol. 2016;67:1214-1226. https://doi.org/10.1016/j.jacc.2015.12.051.

[3]	Habash NW, Sehrawat TS, Shah VH, Cao S. Epigenetics of alcohol-related liver diseases. JHEP Rep. 2022;4:100466. https://doi.org/10.1016/j.jhepr.2022.100466.

[4]	Panni S, Lovering RC, Porras P, Orchard S. Non-coding RNA regulatory net-works. Biochim Biophys Acta Gene Regul Mech. 2020;1863:194417. https://doi.org/10.1016/j.bbagrm.2019.194417.

[5]	Wei JW, Huang K, Yang C, Kang CS. Non-coding RNAs as regulators in epi-genetics (Review). Oncol Rep. 2017;37:3-9. https://doi.org/10.3892/or.2016.5236.

[6]	Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identiﬁcation of novel genes coding for small expressed RNAs. Science. 2001;294:853-858. https://doi.org/10.1126/science.1064921.

[7]	Xu T, Li L, Hu HQ, et al. MicroRNAs in alcoholic liver disease: recent advances and future applications. J Cell Physiol. 2018;234:382-394. https://doi.org/10.1002/jcp.26938.

[8]	Torres JL, Novo-Veleiro I, Manzanedo L, et al. Role of microRNAs in alcohol-induced liver disorders and non-alcoholic fatty liver disease. World J Gastro-enterol. 2018;24:4104-4118. https://doi.org/10.3748/wjg.v24.i36.4104.

[9]	Chen W, Yan X, Yang A, Xu A, Huang T, You H. miRNA-150-5p promotes hepatic stellate cell proliferation and sensitizes hepatocyte apoptosis during liver ﬁbrosis. Epigenomics. 2020;12:53-67. https://doi.org/10.2217/epi-2019-0104.

[10]	Liu CH, Jiang W, Zeng Q, et al. CircRNA-PI4KB induces hepatic lipid deposition in non-alcoholic fatty liver disease by transporting miRNA-122 to extra-he-patocytes. Int J Mol Sci. 2023;24:1297. https://doi.org/10.3390/ijms24021297.

[11]	Mirzaei R, Karampoor S, Korotkova NL. The emerging role of miRNA-122 in infectious diseases: mechanisms and potential biomarkers. Pathol Res Pract. 2023;249:154725. https://doi.org/10.1016/j.prp.2023.154725.

[12]	Zulian V, Fiscon G, Paci P, Garbuglia AR. Hepatitis B virus and microRNAs: a bioinformatics approach. Int J Mol Sci. 2023;24:17224. https://doi.org/10.3390/ijms242417224.

[13]	Wu MN, Sun JY, Yao M, Yao DF. Hepatocellular carcinoma-derived exosomal miRNA expression and its clinical value (in Chinese). Zhonghua Gan Zang Bing Za Zhi. 2020;28:83-86. https://doi.org/10.3760/cma.j.issn.1007-3418.2020.01.020.

[14]	Otsuka M, Kishikawa T, Yoshikawa T, et al. MicroRNAs and liver disease. J Hum Genet. 2017;62:75-80. https://doi.org/10.1038/jhg.2016.53.

[15]	Lee E, Navadurong H, Liangpunsakul S. Epidemiology and trends of alcohol use disorder and alcohol-associated liver disease. Clin Liver Dis (Hoboken). 2023;22:99e102. https://doi.org/10.1097/CLD.0000000000000058.

[16]	Sozio MS, Liangpunsakul S, Crabb D. The role of lipid metabolism in the pathogenesis of alcoholic and nonalcoholic hepatic steatosis. Semin Liver Dis. 2010;30:378-390. https://doi.org/10.1055/s-0030-1267538.

[17]	Mackowiak B, Fu Y, Maccioni L, Gao B. Alcohol-associated liver disease. J Clin Invest. 2024;134:e176345. https://doi.org/10.1172/JCI176345.

[18]	Ma J, Guillot A, Yang Z, et al. Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure. J Clin Invest. 2022;132:e157780. https://doi.org/10.1172/JCI157780.

[19]	Mandrekar P, Bataller R, Tsukamoto H, Gao B. Alcoholic hepatitis: trans-lational approaches to develop targeted therapies. Hepatology. 2016;64: 1343-1355. https://doi.org/10.1002/hep.28530.

[20]	Gao H, Jiang Y, Zeng G, et al. Cell-to-cell and organ-to-organ crosstalk in the pathogenesis of alcohol-associated liver disease. eGastroenterology. 2024;2: e100104. https://doi.org/10.1136/egastro-2024-100104.

[21]	Yang Z, Zhang T, Kusumanchi P, et al. Transcriptomic analysis reveals the microRNAs responsible for liver regeneration associated with mortality in alcohol-associated hepatitis. Hepatology. 2021;74:2436-2451. https://doi.org/10.1002/hep.31994.

[22]	Li M, He Y, Zhou Z, et al. MicroRNA-223 ameliorates alcoholic liver injury by inhibiting the IL-6-p47(phox)-oxidative stress pathway in neutrophils. Gut. 2017;66:705e715. https://doi.org/10.1136/gutjnl-2016-311861.

[23]	Li HD, Du XS, Huang HM, et al. Noncoding RNAs in alcoholic liver disease. J Cell Physiol. 2019;234:14709-14720. https://doi.org/10.1002/jcp.28229.

[24]	Sengupta D, Cassel T, Teng KY, et al. Regulation of hepatic glutamine meta-bolism by miR-122. Mol Metab. 2020;34:174-186. https://doi.org/10.1016/j.molmet.2020.01.003.

[25]	Fernández-Hernando C, Ramírez CM, Goedeke L, Suárez Y. MicroRNAs in metabolic disease. Arterioscler Thromb Vasc Biol. 2013;33:178-185. https://doi.org/10.1161/ATVBAHA.112.300144.

[26]	Ambade A, Satishchandran A, Szabo G. Alcoholic hepatitis accelerates early hepatobiliary cancer by increasing stemness and miR-122-mediated HIF-1a activation. Sci Rep. 2016;6:21340. https://doi.org/10.1038/srep21340.

[27]	Wan Y, McDaniel K, Wu N, et al. Regulation of cellular senescence by miR-34a in alcoholic liver injury. Am J Pathol. 2017;187:2788-2798. https://doi.org/10.1016/j.ajpath.2017.08.027.

[28]	Cao J. The functional role of long non-coding RNAs and epigenetics. Biol Proced Online. 2014;16:11. https://doi.org/10.1186/1480-9222-16-11.

[29]	Caputa G, Schaffer JE. RNA regulation of lipotoxicity and metabolic stress. Diabetes. 2016;65:1816-1823. https://doi.org/10.2337/db16-0147.

[30]	Yang Z, Jiang Y, Ma J, et al. LncRNA H 19 promoted alcohol-associated liver disease through dysregulation of alternative splicing and methionine meta-bolism. Hepatology. 2024. https://doi.org/10.1097/HEP.0000000000001078.

[31]	Wang G, Tong J, Li Y, et al. Overview of circRNAs roles and mechanisms in liver ﬁbrosis. Biomolecules. 2023;13:940. https://doi.org/10.3390/biom13060940.

[32]	Hansen TB, Jensen TI, Clausen BH, et al. Natural RNA circles function as efﬁ-cient microRNA sponges. Nature. 2013;495:384-388. https://doi.org/10.1038/nature11993.

[33]	Lu X, Liu Y, Xuan W, et al. Circ_ 1639 induces cells inflammation responses by sponging miR-122 and regulating TNFRSF13C expression in alcoholic liver disease. Toxicol Lett. 2019;314:89-97. https://doi.org/10.1016/j.toxlet.2019.07.021.

[34]	Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843-854. https://doi.org/10.1016/0092-8674(93)90529-y.

[35]	He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522-531. https://doi.org/10.1038/nrg1379.

[36]	O’Brien J, Hayder H, Zayed Y, Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol (Lausanne). 2018;9:402. https://doi.org/10.3389/fendo.2018.00402.

[37]	Macfarlane LA, Murphy PR. MicroRNA: biogenesis, function and role in cancer. Curr Genomics. 2010;11:537e561. https://doi.org/10.2174/138920210793175895.

[38]	Dhir A, Dhir S, Proudfoot NJ, Jopling CL. Microprocessor mediates transcrip-tional termination of long noncoding RNA transcripts hosting microRNAs. Nat Struct Mol Biol. 2015;22:319-327. https://doi.org/10.1038/nsmb.2982.

[39]	Yeom KH, Lee Y, Han J, Suh MR, Kim VN. Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing. Nucleic Acids Res. 2006;34:4622-4629. https://doi.org/10.1093/nar/gkl458.

[40]	Katahira J, Yoneda Y. Nucleocytoplasmic transport of microRNAs and related small RNAs. Trafﬁc. 2011;12:1468-1474. https://doi.org/10.1111/j.1600-0854.2011.01211.x.

[41]	Medley JC, Panzade G, Zinovyeva AY. microRNA strand selection: unwinding the rules. Wiley Interdiscip Rev RNA. 2021;12:e1627. https://doi.org/10.1002/wrna.1627.

[42]	Ameres SL, Zamore PD. Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol. 2013;14:475e488. https://doi.org/10.1038/nrm3611.

[43]	Gregory RI, Yan KP, Amuthan G, et al. The Microprocessor complex mediates the genesis of microRNAs. Nature. 2004;432:235-240. https://doi.org/10.1038/nature03120.

[44]	Maniataki E, Mourelatos Z. A human, ATP-independent, RISC assembly ma-chine fueled by pre-miRNA. Genes Dev. 2005;19:2979-2990. https://doi.org/10.1101/gad.1384005.

[45]	Okamura K, Hagen JW, Duan H, Tyler DM, Lai EC. The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell. 2007;130: 89-100. https://doi.org/10.1016/j.cell.2007.06.028.

[46]	Yang JS, Lai EC. Alternative miRNA biogenesis pathways and the interpreta-tion of core miRNA pathway mutants. Mol Cell. 2011;43:892-903. https://doi.org/10.1016/j.molcel.2011.07.024.

[47]	Valinezhad Orang A, Safaralizadeh R, Kazemzadeh-Bavili M. Mechanisms of miRNA-mediated gene regulation from common downregulation to mRNA-speciﬁc upregulation. Int J Genomics. 2014;2014:970607. https://doi.org/10.1155/2014/970607.

[48]	Wang X, He Y, Mackowiak B, Gao B. MicroRNAs as regulators, biomarkers and therapeutic targets in liver diseases. Gut. 2021;70:784-795. https://doi.org/10.1136/gutjnl-2020-322526.

[49]	Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science. 2007;318:1931-1934. https://doi.org/10.1126/science.1149460.

[50]	Zhang J, Li S, Li L, et al. Exosome and exosomal microRNA: trafﬁcking, sorting, and function. Genomics Proteomics Bioinformatics. 2015;13:17-24. https://doi.org/10.1016/j.gpb.2015.02.001.

[51]	Fabbiano F, Corsi J, Gurrieri E, Trevisan C, Notarangelo M, D’Agostino VG. RNA packaging into extracellular vesicles: an orchestra of RNA-binding proteins? J Extracell Vesicles. 2020;10:e12043. https://doi.org/10.1002/jev2.12043.

[52]	Correia CN, Nalpas NC, McLoughlin KE, et al. Circulating microRNAs as po-tential biomarkers of infectious disease. Front Immunol.. 2017;8:118. https://doi.org/10.3389/ﬁmmu.2017.00118.

[53]	Kumarswamy R, Volkmann I, Thum T. Regulation and function of miRNA-21 in health and disease. RNA Biol. 2011;8:706-713. https://doi.org/10.4161/rna.8.5.16154.

[54]	Zhang T, Yang Z, Kusumanchi P, Han S, Liangpunsakul S. Critical role of microRNA-21 in the pathogenesis of liver diseases. Front Med (Lausanne). 2020;7:7. https://doi.org/10.3389/fmed.2020.00007.

[55]	Ha TY. MicroRNAs in human diseases: from lung, liver and kidney diseases to infectious disease, sickle cell disease and endometrium disease. Immune Netw. 2011;11:309-323. https://doi.org/10.4110/in.2011.11.6.309.

[56]	Jenike AE, Halushka MK. miR-21: a non-speciﬁc biomarker of all maladies. Biomark Res. 2021;9:18. https://doi.org/10.1186/s40364-021-00272-1.

[57]	Zhu H, Luo H, Li Y, et al. MicroRNA-21 in scleroderma ﬁbrosis and its function in TGF-beta-regulated ﬁbrosis-related genes expression. J Clin Immunol. 2013;33:1100-1109. https://doi.org/10.1007/s10875-013-9896-z.

[58]	Beltrami C, Besnier M, Shantikumar S, et al. Human pericardial fluid contains exosomes enriched with cardiovascular-expressed microRNAs and promotes therapeutic angiogenesis. Mol Ther. 2017;25:679-693. https://doi.org/10.1016/j.ymthe.2016.12.022.

[59]	McDaniel K, Herrera L, Zhou T, et al. The functional role of microRNAs in alcoholic liver injury. J Cell Mol Med. 2014;18:197e207. https://doi.org/10.1111/jcmm.12223.

[60]	Francis H, McDaniel K, Han Y, et al. Regulation of the extrinsic apoptotic pathway by microRNA-21 in alcoholic liver injury. J Biol Chem. 2014;289: 27526-27539. https://doi.org/10.1074/jbc.M114.602383.

[61]	Selaru FM, Olaru AV, Kan T, et al. MicroRNA-21 is overexpressed in human cholangiocarcinoma and regulates programmed cell death 4 and tissue in-hibitor of metalloproteinase 3. Hepatology. 2009;49:1595-1601. https://doi.org/10.1002/hep.22838.

[62]	Wang ZX, Lu BB, Wang H, Cheng ZX, Yin YM. MicroRNA-21 modulates che-mosensitivity of breast cancer cells to doxorubicin by targeting PTEN. Arch Med Res. 2011;42:281-290. https://doi.org/10.1016/j.arcmed.2011.06.008.

[63]	Oka S, Li X, Zhang F, et al. MicroRNA-21 facilitates osteoblast activity. Biochem Biophys Rep. 2021;25:100894. https://doi.org/10.1016/j.bbrep.2020.100894.

[64]	Sun C, Huang F, Liu X, et al. miR-21 regulates triglyceride and cholesterol metabolism in non-alcoholic fatty liver disease by targeting HMGCR. Int J Mol Med. 2015;35:847e853. https://doi.org/10.3892/ijmm.2015.2076.

[65]	Wu N, McDaniel K, Zhou T, et al. Knockout of microRNA-21 attenuates alco-holic hepatitis through the VHL/NF-kB signaling pathway in hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol. 2018;315:G385eG398. https://doi.org/10.1152/ajpgi.00111.2018.

[66]	Srivastava A, Parrish A, Hoek JB, Vadigepalli R. Modulation of miR-21 can reprogram the TGF-b signaling pathway to alter HSC phenotype in vitro. FASEB J. 2022; 36(suppl 1). https://doi.org/10.1096/fasebj.2022.36.S1.R5237.

[67]	Jouve M, Carpentier R, Kraiem S, Legrand N, Sobolewski C. MiRNAs in alcohol-related liver diseases and hepatocellular carcinoma: a step toward new therapeutic approaches? Cancers (Basel). 2023;15:5557. https://doi.org/10.3390/cancers15235557.

[68]	Kota J, Chivukula RR, O’Donnell KA, et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell. 2009;137: 1005-1017. https://doi.org/10.1016/j.cell.2009.04.021.

[69]	Zhang J, Han C, Wu T. MicroRNA-26a promotes cholangiocarcinoma growth by activating b-catenin. Gastroenterology. 2012;143:246e 256 (e8). https://doi.org/10.1053/j.gastro.2012.03.045.

[70]	Witwer KW, Sisk JM, Gama L, Clements JE. MicroRNA regulation of IFN-beta protein expression: rapid and sensitive modulation of the innate immune response. J Immunol. 2010;184:2369-2376. https://doi.org/10.4049/jimmunol.0902712.

[71]	Zhou J, Ju W, Wang D, et al. Down-regulation of microRNA-26a promotes mouse hepatocyte proliferation during liver regeneration. PLoS One. 2012;7: e33577. https://doi.org/10.1371/journal.pone.0033577.

[72]	Han W, Fu X, Xie J, et al. MiR-26a enhances autophagy to protect against ethanol-induced acute liver injury. J Mol Med (Berl). 2015;93:1045-1055. https://doi.org/10.1007/s00109-015-1282-2.

[73]	Saha B, Bruneau JC, Kodys K, Szabo G. Alcohol-induced miR-27a regulates differentiation and M2 macrophage polarization of normal human mono-cytes. J Immunol. 2015;194:3079-3087. https://doi.org/10.4049/jimmunol.1402190.

[74]	Saha B, Momen-Heravi F, Kodys K, Szabo G. MicroRNA cargo of extracellular vesicles from alcohol-exposed monocytes signals naive monocytes to differ-entiate into M2 macrophages. J Biol Chem. 2016;291:149e159. https://doi.org/10.1074/jbc.M115.694133.

[75]	Ju C, Liangpunsakul S. Role of hepatic macrophages in alcoholic liver disease. J Investig Med. 2016;64:1075-1077. https://doi.org/10.1136/jim-2016-000210.

[76]	Tsuchiya K, Suzuki Y, Yoshimura K, et al. Macrophage mannose receptor CD 206 predicts prognosis in community-acquired pneumonia. Sci Rep. 2019;9:18750. https://doi.org/10.1038/s41598-019-55289-2.

[77]	Santos-Bezerra DP, Cavaleiro AM, Santos AS, et al. Alcohol use disorder is associated with upregulation of microRNA-34a and microRNA-34c in hippo-campal postmortem tissue. Alcohol Clin Exp Res. 2021;45:64-68. https://doi.org/10.1111/acer.14505.

[78]	Piccolo P, Ferriero R, Barbato A, et al. Up-regulation of miR-34b/c by JNK and FOXO 3 protects from liver ﬁbrosis. Proc Natl Acad Sci U S A. 2021;118: e2025242118. https://doi.org/10.1073/pnas.2025242118.

[79]	Liu H, French BA, Li J, Tillman B, French SW. Altered regulation of miR-34a and miR-483-3p in alcoholic hepatitis and DDC fed mice. Exp Mol Pathol. 2015;99: 552-557. https://doi.org/10.1016/j.yexmp.2015.09.005.

[80]	Misso G, Di Martino MT, De Rosa G, et al. Mir-34: a new weapon against cancer? Mol Ther Nucleic Acids. 2014;3:e194. https://doi.org/10.1038/mtna.2014.47.

[81]	Wan Y, Slevin E, Koyama S, et al. miR-34a regulates macrophage-associated inflammation and angiogenesis in alcohol-induced liver injury. Hepatol Commun. 2023;7:e0089. https://doi.org/10.1097/hc9.0000000000000089.

[82]	Meng F, Glaser SS, Francis H, et al. Epigenetic regulation of miR-34a expres-sion in alcoholic liver injury. Am J Pathol. 2012;181:804-817. https://doi.org/10.1016/j.ajpath.2012.06.010.

[83]	Iwagami Y, Zou J, Zhang H, et al. Alcohol-mediated miR-34a modulates he-patocyte growth and apoptosis. J Cell Mol Med. 2018;22:3987-3995. https://doi.org/10.1111/jcmm.13681.

[84]	Yamakuchi M, Ferlito M, Lowenstein CJ. miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci U S A. 2008;105:13421-13426. https://doi.org/10.1073/pnas.0801613105.

[85]	Li N, Fu H, Tie Y, et al. miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett. 2009;275:44-53. https://doi.org/10.1016/j.canlet.2008.09.035.

[86]	Sun F, Fu H, Liu Q, et al. Downregulation of CCND1 and CDK 6 by miR-34a induces cell cycle arrest. FEBS Lett. 2008;582:1564e1568. https://doi.org/10.1016/j.febslet.2008.03.057.

[87]	Raver-Shapira N, Marciano E, Meiri E, et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell. 2007;26:731e743. https://doi.org/10.1016/j.molcel.2007.05.017.

[88]	Jopling C. Liver-speciﬁc microRNA-122: biogenesis and function. RNA Biol. 2012;9:137e142. https://doi.org/10.4161/rna.18827.

[89]	Xu H, He JH, Xiao ZD, et al. Liver-enriched transcription factors regulate microRNA-122 that targets CUTL 1 during liver development. Hepatology. 2010;52:1431-1442. https://doi.org/10.1002/hep.23818.

[90]	Satishchandran A, Ambade A, Rao S, et al. MicroRNA 122, regulated by GRLH2, protects livers of mice and patients from ethanol-induced liver disease. Gastroenterology. 2018;154:238e 252 (e7). https://doi.org/10.1053/j.gastro.2017.09.022.

[91]	Bala S, Babuta M, Catalano D, Saiju A, Szabo G. Alcohol promotes exosome biogenesis and release via modulating Rabs and miR-192 expression in hu-man hepatocytes. Front Cell Dev Biol. 2021;9:787356. https://doi.org/10.3389/fcell.2021.787356.

[92]	Wen J, Friedman JR. miR-122 regulates hepatic lipid metabolism and tumor suppression. J Clin Invest. 2012;122:2773-2776. https://doi.org/10.1172/jci63966.

[93]	Yang Z, Cappello T, Wang L. Emerging role of microRNAs in lipid metabolism. Acta Pharm Sin B. 2015;5:145e150. https://doi.org/10.1016/j.apsb.2015.01.002.

[94]	Pasqualotto A, Ayres R, Longo L, et al. Chronic exposure to ethanol alters the expression of miR-155, miR-122 and miR-217 in alcoholic liver disease in an adult zebraﬁsh model. Biomarkers. 2021;26:146e151. https://doi.org/10.1080/1354750X.2021.1874051.

[95]

Luo HY, Li G, Liu YG, et al. The accelerated progression of atherosclerosis correlates with decreased miR-33a and miR-21 and increased miR-122 and miR-3064-5p in circulation and the liver of ApoE-/- mice with streptozocin (STZ)-induced type 2 diabetes. Curr Issues Mol Biol. 2022;44:4822-4837. https://doi.org/10.3390/cimb44100328.

[96]	Zinkhan EK, Yu B, Schlegel A. Prenatal exposure to a maternal high fat diet increases hepatic cholesterol accumulation in intrauterine growth restricted rats in part through microRNA-122 inhibition of Cyp7a1. Front Physiol. 2018;9:645. https://doi.org/10.3389/fphys.2018.00645.

[97]

Elseweidy MM, Elawady AS, Sobh MS, Alqhtani AH, Al-Gabri NA, Elnagar GM. Potential of caffeic acid and 10-dehydrogingerdione as lipid regulators rele-vant to their inhibitory effect on miR-122 and ATP citrate lyase activity in diabetic hyperlipidemic rats. Biomedicines. 2023;11:726. https://doi.org/10.3390/biomedicines11030726.

[98]	Esau C, Davis S, Murray SF, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006;3:87-98. https://doi.org/10.1016/j.cmet.2006.01.005.

[99]	Girard M, Jacquemin E, Munnich A, Lyonnet S, Henrion-Caude A. miR-122, a paradigm for the role of microRNAs in the liver. J Hepatol. 2008;48:648-656. https://doi.org/10.1016/j.jhep.2008.01.019.

[100]

Teng KY, Barajas JM, Hu P, Jacob ST, Ghoshal K. Role of B cell lymphoma 2 in the regulation of liver ﬁbrosis in miR-122 knockout mice. Biology (Basel). 2020;9:157. https://doi.org/10.3390/biology9070157.

[101]

Long JK, Dai W, Zheng YW, Zhao SP. miR-122 promotes hepatic lipogenesis via inhibiting the LKB1/AMPK pathway by targeting Sirt1 in non-alcoholic fatty liver disease. Mol Med. 2019;25:26. https://doi.org/10.1186/s10020-019-0085-2.

[102]

Coulouarn C, Factor VM, Andersen JB, Durkin ME, Thorgeirsson SS. Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene. 2009;28:3526-3536. https://doi.org/10.1038/onc.2009.211.

[103]

Kishikawa T, Otsuka M, Tan PS, et al. Decreased miR122 in hepatocellular carcinoma leads to chemoresistance with increased arginine. Oncotarget. 2015;6:8339-8352. https://doi.org/10.18632/oncotarget.3234.

[104]

Bai S, Nasser MW, Wang B, et al. MicroRNA-122 inhibits tumorigenic prop-erties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem. 2009;284:32015e32027. https://doi.org/10.1074/jbc.M109.016774.

[105]

Lee JS, Chu IS, Heo J, et al. Classiﬁcation and prediction of survival in hepa-tocellular carcinoma by gene expression proﬁling. Hepatology. 2004;40: 667-676. https://doi.org/10.1002/hep.20375.

[106]

Momen-Heravi F, Bala S, Kodys K, Szabo G. Exosomes derived from alcohol-treated hepatocytes horizontally transfer liver speciﬁc miRNA-122 and sensitize monocytes to LPS. Sci Rep. 2015;5:9991. https://doi.org/10.1038/srep09991.

[107]

Shen Z, Ajmo JM, Rogers CQ, et al. Role of SIRT 1 in regulation of LPS- or two ethanol metabolites-induced TNF-alpha production in cultured macrophage cell lines. Am J Physiol Gastrointest Liver Physiol. 2009;296:G1047eG1053. https://doi.org/10.1152/ajpgi.00016.2009.

[108]

Blaya D, Aguilar-Bravo B, Hao F, et al. Expression of microRNA-155 in in-flammatory cells modulates liver injury. Hepatology. 2018;68:691e706. https://doi.org/10.1002/hep.29833.

[109]

Bala S, Szabo G. MicroRNA signature in alcoholic liver disease. Int J Hepatol. 2012;2012:498232. https://doi.org/10.1155/2012/498232.

[110]

Rodriguez A, Vigorito E, Clare S, et al. Requirement of bic/microRNA-155 for normal immune function. Science. 2007;316:608e611. https://doi.org/10.1126/science.1139253.

[111]

O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA. 2007;104:1604-1609. https://doi.org/10.1073/pnas.0610731104.

[112]

Wang B, Majumder S, Nuovo G, et al. Role of microRNA-155 at early stages of hepatocarcinogenesis induced by choline-deﬁcient and amino acid-deﬁned diet in C57BL/ 6 mice. Hepatology. 2009;50:1152-1161. https://doi.org/10.1002/hep.23100.

[113]

Bala S, Marcos M, Kodys K, et al. Up-regulation of microRNA-155 in mac-rophages contributes to increased tumor necrosis factor {alpha} (TNF {alpha}) production via increased mRNA half-life in alcoholic liver disease. JBiolChem. 2011;286:1436-1444. https://doi.org/10.1074/jbc.M110.14 5870.

[114]

Fuseler JW, Merrill DM, Rogers JA, Grisham MB, Wolf RE. Analysis and quantitation of NF-kappaB nuclear translocation in tumor necrosis factor alpha (TNF-alpha) activated vascular endothelial cells. Microsc Microanal. 2006;12:269-276. https://doi.org/10.1017/s1431927606060260.

[115]

Bala S, Csak T, Saha B, et al. The pro-inflammatory effects of miR-155 promote liver ﬁbrosis and alcohol-induced steatohepatitis. J Hepatol. 2016;64: 1378-1387. https://doi.org/10.1016/j.jhep.2016.01.035.

[116]

Babuta M, Furi I, Bala S, et al. Dysregulated autophagy and lysosome func-tion are linked to exosome production by micro-RNA 155 in alcoholic liver disease. Hepatology. 2019;70:2123-2141. https://doi.org/10.1002/hep.30766.

[117]

Wan G, Xie W, Liu Z, et al. Hypoxia-induced MIR155 is a potent autophagy inducer by targeting multiple players in the MTOR pathway. Autophagy. 2014;10:70-79. https://doi.org/10.4161/auto.26534.

[118]

Saikia P, Bellos D, McMullen MR, Pollard KA, de la Motte C, Nagy LE. MicroRNA 181b-3p and its target importin a5 regulate toll-like receptor 4 signaling in Kupffer cells and liver injury in mice in response to ethanol. Hepatology. 2017;66:602-615. https://doi.org/10.1002/hep.29144.

[119]

Wang W, Zhong GZ, Long KB, Liu Y, Liu YQ, Xu AL. Silencing miR-181b-5p upregulates PIAS1 to repress oxidative stress and inflammatory response in rats with alcoholic fatty liver disease through inhibiting PRMT1. Int Immu-nopharmacol. 2021;101:108151. https://doi.org/10.1016/j.intimp.2021.108151.

[120]

Wang Y, Zhu K, Yu W, et al. MiR-181b regulates steatosis in nonalcoholic fatty liver disease via targeting SIRT1. Biochem Biophys Res Commun. 2017;493: 227-232. https://doi.org/10.1016/j.bbrc.2017.09.042.

[121]

Blaya D, Coll M, Rodrigo-Torres D, et al. Integrative microRNA proﬁling in alcoholic hepatitis reveals a role for microRNA-182 in liver injury and inflammation. Gut. 2016;65:1535-1545. https://doi.org/10.1136/gutjnl-2015-311314.

[122]

Zuo Z, Li Y, Zeng C, Xi Y, Tao H, Guo Y. Integrated analyses identify key molecules and reveal the potential mechanism of miR-182-5p/FOXO1 axis in alcoholic liver disease. Front Med (Lausanne). 2021;8:767584. https://doi.org/10.3389/fmed.2021.767584.

[123]

Yang W, Kim DM, Jiang W, et al. Suppression of FOXO 1 attenuates inflamm-aging and improves liver function during aging. Aging Cell. 2023;22:e13968. https://doi.org/10.1111/acel.13968.

[124]

Meng Z, Fu X, Chen X, et al. miR-194 is a marker of hepatic epithelial cells and suppresses metastasis of liver cancer cells in mice. Hepatology. 2010;52: 2148-2157. https://doi.org/10.1002/hep.23915.

[125]

Dong R, Wang X, Wang L, et al. Yangonin inhibits ethanol-induced hepatocyte senescence via miR-194/FXR axis. Eur J Pharmacol. 2021;890:173653. https://doi.org/10.1016/j.ejphar.2020.173653.

[126]

Jiang M, Li F, Liu Y, et al. Probiotic-derived nanoparticles inhibit ALD through intestinal miR194 suppression and subsequent FXR activation. Hepatology. 2023;77:1164-1180. https://doi.org/10.1002/hep.32608.

[127]

Gilicze AB, Wiener Z, Tóth S, et al. Myeloid-derived microRNAs, miR-223, miR27a, and miR-652, are dominant players in myeloid regulation. Biomed Res Int. 2014;2014:870267. https://doi.org/10.1155/2014/870267.

[128]

Ren R, He Y, Ding D, et al. Aging exaggerates acute-on-chronic alcohol-induced liver injury in mice and humans by inhibiting neutrophilic sirtuin 1-C/EBPa-miRNA-223 axis. Hepatology. 2022;75:646e660. https://doi.org/10.1002/hep.32152.

[129]

Aziz F. The emerging role of miR-223 as novel potential diagnostic and therapeutic target for inflammatory disorders. Cell Immunol. 2016;303:1-6. https://doi.org/10.1016/j.cellimm.2016.04.003.

[130]

Haneklaus M, Gerlic M, O’Neill LA, Masters SL.miR-223: infection, inflam-mation and cancer. J Intern Med. 2013;274:215-226. https://doi.org/10.1111/joim.12099.

[131]

Dong X, Liu H, Chen F, Li D, Zhao Y. MiR-214 promotes the alcohol-induced oxidative stress via down-regulation of glutathione reductase and cyto-chrome P450 oxidoreductase in liver cells. Alcohol Clin Exp Res. 2014;38: 68-77. https://doi.org/10.1111/acer.12209.

[132]

Herrnreiter CJ, Luck ME, Cannon AR, Li X, Choudhry MA. Reduced expression of miR-146a potentiates intestinal inflammation following alcohol and burn injury. J Immunol. 2024;212:881-893. https://doi.org/10.4049/jimmunol.2300405.

[133]

Dasgupta D, Ghosh S, Dey I, et al. Influence of polymorphisms in TNF-a and IL1b on susceptibility to alcohol induced liver diseases and therapeutic po-tential of miR-124-3p impeding TNF-a/IL1b mediated multi-cellular signaling in liver microenvironment. Front Immunol. 2023;14:1241755. https://doi.org/10.3389/ﬁmmu.2023.1241755.

[134]

Zhou K, Yin F, Li Y, et al. MicroRNA-29b ameliorates hepatic inflammation via suppression of STAT3 in alcohol-associated liver disease. Alcohol. 2022;99: 9-22. https://doi.org/10.1016/j.alcohol.2021.10.003.

[135]

Cheng XY, Liu JD, Lu XY, et al. miR-203 inhibits alcohol-induced hepatic steatosis by targeting Lipin1. Front Pharmacol. 2018;9:275. https://doi.org/10.3389/fphar.2018.00275.

[136]

Yin H, Liang X, Jogasuria A, Davidson NO, You M. miR-217 regulates ethanol-induced hepatic inflammation by disrupting sirtuin 1-lipin-1 signaling. Am J Pathol. 2015;185:1286-1296. https://doi.org/10.1016/j.ajpath.2015.01.030.

[137]

Yin H, Hu M, Zhang R, Shen Z, Flatow L, You M. MicroRNA-217 promotes ethanol-induced fat accumulation in hepatocytes by down-regulating SIRT1. J Biol Chem. 2012;287:9817-9826. https://doi.org/10.1074/jbc.M111.333534.

[138]

Ye J, Lin Y, Yu Y, Sun D. LncRNA NEAT1/microRNA-129-5p/SOCS2 axis regu-lates liver ﬁbrosis in alcoholic steatohepatitis. J Transl Med. 2020;18:445. https://doi.org/10.1186/s12967-020-02577-5.

[139]

Chen Y, Ou Y, Dong J, et al. Osteopontin promotes collagen I synthesis in hepatic stellate cells by miRNA-129-5p inhibition. Exp Cell Res. 2018;362: 343-348. https://doi.org/10.1016/j.yexcr.2017.11.035.

[140]

Brandon-Warner E, Benbow JH, Swet JH, et al. Adeno-associated virus sero-type 2 vector-mediated reintroduction of microRNA-19b attenuates hepatic ﬁbrosis. Hum Gene Ther. 2018;29:674-686. https://doi.org/10.1089/hum.2017.035.

[141]

Emmrich S, Katsman-Kuipers JE, Henke K, et al. miR-9 is a tumor suppressor in pediatric AML with t(8;21). Leukemia. 2014;28:1022-1032. https://doi.org/10.1038/leu.2013.357.

[142]

Szabo G, Bala S. Alcoholic liver disease and the gut-liver axis. World J Gas-troenterol. 2010;16:1321-1329. https://doi.org/10.3748/wjg.v16.i11.1321.

[143]

Tang Y, Zhang L, Forsyth CB, Shaikh M, Song S, Keshavarzian A. The role of miR-212 and iNOS in alcohol-induced intestinal barrier dysfunction and steatohepatitis. Alcohol Clin Exp Res. 2015;39:1632-1641. https://doi.org/10.1111/acer.12813.

[144]

Tang Y, Banan A, Forsyth CB, et al. Effect of alcohol on miR-212 expression in intestinal epithelial cells and its potential role in alcoholic liver disease. Alcohol Clin Exp Res. 2008;32:355e364. https://doi.org/10.1111/j.1530-0277.2007.00584.x.

[145]

Luo J, Hou Y, Ma W, et al. A novel mechanism underlying alcohol dehydro-genase expression: hsa-miR-148a-3p promotes ADH 4 expression via an AGO1-dependent manner in control and ethanol-exposed hepatic cells. Bio-chem Pharmacol. 2021;189:114458. https://doi.org/10.1016/j.bcp.2021.114458.

[146]

Heo MJ, Kim TH, You JS, Blaya D, Sancho-Bru P, Kim SG. Alcohol dysregulates miR-148a in hepatocytes through FoxO1, facilitating pyroptosis via TXNIP overexpression. Gut. 2019;68:708-720. https://doi.org/10.1136/gutjnl-2017-315123.

[147]

Shihana F, Joglekar MV, Schwantes-An TH, Hardikar AA, Seth D. MicroRNAs signature panel identiﬁes heavy drinkers with alcohol-associated cirrhosis from heavy drinkers without liver injury. Biology (Basel). 2023;12:1314. https://doi.org/10.3390/biology12101314.

[148]

Luo J, Ji Y, Chen N, et al. Nuclear miR-150 enhances hepatic lipid accumulation by targeting RNA transcripts overlapping the PLIN2 promoter. iScience. 2023;26:107837. https://doi.org/10.1016/j.isci.2023.107837.

[149]

Yeligar S, Tsukamoto H, Kalra VK.Ethanol-induced expression of ET-1 and ET-BR in liver sinusoidal endothelial cells and human endothelial cells involves hypoxia-inducible factor-1alpha and microrNA-199. J Immunol. 2009;183: 5232-5243. https://doi.org/10.4049/jimmunol.0901084.

[150]

Zhao YX, Sun YY, Huang AL, et al. MicroRNA-200a induces apoptosis by tar-geting ZEB 2 in alcoholic liver disease. Cell Cycle. 2018;17:250e262. https://doi.org/10.1080/15384101.2017.1417708.

[151]

Saikia P, Roychowdhury S, Bellos D, et al. Hyaluronic acid 35 normalizes TLR4 signaling in Kupffer cells from ethanol-fed rats via regulation of micro-RNA291b and its target Tollip. Sci Rep. 2017;7:15671. https://doi.org/10.1038/s41598-017-15760-4.

[152]

Kim YD, Hwang SL, Lee EJ, et al. Melatonin ameliorates alcohol-induced bile acid synthesis by enhancing miR-497 expression. J Pineal Res. 2017; 62. https://doi.org/10.1111/jpi.12386..

[153]

McDaniel K, Huang L, Sato K, et al. The let-7/Lin 28 axis regulates activation of hepatic stellate cells in alcoholic liver injury. J Biol Chem. 2017;292: 11336-11347. https://doi.org/10.1074/jbc.M116.773291.

[154]

Bridges MC, Daulagala AC, Kourtidis A. LNCcation: lncRNA localization and function. J Cell Biol. 2021;220:e202009045. https://doi.org/10.1083/jcb.202009045.

[155]

Herman AB, Tsitsipatis D, Gorospe M. Integrated lncRNA function upon genomic and epigenomic regulation. Mol Cell. 2022;82:2252-2266. https://doi.org/10.1016/j.molcel.2022.05.027.

[156]

Tan YT, Lin JF, Li T, Li JJ, Xu RH, Ju HQ. LncRNA-mediated posttranslational modiﬁcations and reprogramming of energy metabolism in cancer. Cancer Commun (Lond). 2021;41:109e120. https://doi.org/10.1002/cac2.12108.

[157]

Derrien T, Johnson R, Bussotti G, et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 2012;22:1775-1789. https://doi.org/10.1101/gr.132159.111.

[158]

Liu SY, Tsai IT, Hsu YC. Alcohol-related liver disease: basic mechanisms and clinical perspectives. Int J Mol Sci. 2021;22:5170. https://doi.org/10.3390/ijms22105170.

[159]

Schmidt K, Weidmann CA, Hilimire TA, et al. Targeting the oncogenic long non-coding RNA SLNCR1 by blocking its sequence-speciﬁc binding to the androgen receptor. Cell Rep. 2020;30:541e 554 (e5). https://doi.org/10.1016/j.celrep.2019.12.011.

[160]

Ahn JH, Lee HS, Lee JS, et al. nc886 is induced by TGF-b and suppresses the microRNA pathway in ovarian cancer. Nat Commun. 2018;9:1166. https://doi.org/10.1038/s41467-018-03556-7.

[161]

Jiang L, Shao C, Wu QJ, et al. NEAT 1 scaffolds RNA-binding proteins and the Microprocessor to globally enhance pri-miRNA processing. Nat Struct Mol Biol. 2017;24:816-824. https://doi.org/10.1038/nsmb.3455.

[162]

Zealy RW, Fomin M, Davila S, et al. Long noncoding RNA complementarity and target transcripts abundance. Biochim Biophys Acta Gene Regul Mech. 2018;1861:224-234. https://doi.org/10.1016/j.bbagrm.2018.02.001.

[163]

Stickel F, Hampe J. Genetic determinants of alcoholic liver disease. Gut. 2012;61:150e159. https://doi.org/10.1136/gutjnl-2011-301239.

[164]

Salameh H, Raff E, Erwin A, et al. PNPLA 3 gene polymorphism is associated with predisposition to and severity of alcoholic liver disease. Am J Gastro-enterol. 2015;110:846-856. https://doi.org/10.1038/ajg.2015.137.

[165]

You M, Arteel GE. Effect of ethanol on lipid metabolism. J Hepatol. 2019;70: 237-248. https://doi.org/10.1016/j.jhep.2018.10.037.

[166]

Higuchi H, Kurose I, Kato S, Miura S, Ishii H. Ethanol-induced apoptosis and oxidative stress in hepatocytes. Alcohol Clin Exp Res. 1996;20:340Ae346A.

[167]

Zhang L, Wang R, Nan Y, Kong L. Deciphering the role of LncRNA in alcoholic liver disease: mechanisms and therapeutic potential. Medicine (Baltimore). 2024;103:e40378. https://doi.org/10.1097/md.0000000000040378.

[168]

Shen S, Wang J, Lin LM. Downregulation of long non-coding RNA AIRN pro-motes mitophagy in alcoholic fatty hepatocytes by promoting ubiquitination of mTOR. Physiol Res. 2021;70:245e253. https://doi.org/10.33549/physiolres.934549.

[169]

Wang Q, Li M, Shen Z, et al. The long non-coding RNA MEG3/miR-let-7c-5p axis regulates ethanol-induced hepatic steatosis and apoptosis by targeting NLRC5. Front Pharmacol. 2018;9:302. https://doi.org/10.3389/fphar.2018.00302.

[170]

Dou X, Yang W, Ding Q, et al. Comprehensive analysis of the expression proﬁles of hepatic lncRNAs in the mouse model of alcoholic liver disease. Front Pharmacol. 2021;12:709287. https://doi.org/10.3389/fphar.2021.709287.

[171]

Liu R, Li X, Zhu W, et al. Cholangiocyte-derived exosomal long noncoding RNA H 19 promotes hepatic stellate cell activation and cholestatic liver ﬁbrosis. Hepatology. 2019;70:1317e1335. https://doi.org/10.1002/hep.30662.

[172]

Xiao Y, Liu R, Li X, et al. Long noncoding RNA H 19 contributes to cholangiocyte proliferation and cholestatic liver ﬁbrosis in biliary atresia. Hepatology. 2019;70:1658-1673. https://doi.org/10.1002/hep.30698.

[173]

Lackner C, Tiniakos D. Fibrosis and alcohol-related liver disease. J Hepatol. 2019;70:294e304. https://doi.org/10.1016/j.jhep.2018.12.003.

[174]

Xia S, Huang Y, Zhang Y, et al. Role of macrophage-to-myoﬁbroblast transition in chronic liver injury and liver ﬁbrosis. Eur J Med Res. 2023;28:502. https://doi.org/10.1186/s40001-023-01488-7.

[175]

Chen D, Lu P, Sun T, Ding A. Long non-coding RNA HOX transcript antisense intergenic RNA depletion protects against alcoholic hepatitis through the microRNA-148a-3p/sphingosine 1-phosphate receptor 1 axis. Cell Tissue Res. 2023;394:471-485. https://doi.org/10.1007/s00441-023-03835-w.

[176]

Zhou B, Yuan W, Li X. LncRNA Gm5091 alleviates alcoholic hepatic ﬁbrosis by sponging miR-27b/23b/24 in mice. Cell Biol Int. 2018;42:1330-1339. https://doi.org/10.1002/cbin.11021.

[177]

Shi X, Jiang X, Yuan B, et al. LINC 01093 upregulation protects against alcoholic hepatitis through inhibition of NF-kB signaling pathway. Mol Ther Nucleic Acids. 2019;17:791-803. https://doi.org/10.1016/j.omtn.2019.06.018.

[178]

Wu Y, Qi Y, Bai Y, et al. LncRNA 1700020I14Rik promotes AKR1B 10 expression and activates Erk pathway to induce hepatocyte damage in alcoholic hepa-titis. Cell Death Discov. 2022;8:374. https://doi.org/10.1038/s41420-022-01135-w.

[179]

Yang Z, Ross RA, Zhao S, Tu W, Liangpunsakul S, Wang L. LncRNA AK054921 and AK128652 are potential serum biomarkers and predictors of patient survival with alcoholic cirrhosis. Hepatol Commun. 2017;1:513e523. https://doi.org/10.1002/hep4.1061.

[180]

Santer L, Bär C, Thum T. Circular RNAs: a novel class of functional RNA mol-ecules with a therapeutic perspective. Mol Ther. 2019;27:1350-1363. https://doi.org/10.1016/j.ymthe.2019.07.001.

[181]

Cocquerelle C, Mascrez B, Hétuin D, Bailleul B. Mis-splicing yields circular RNA molecules. FASEB J. 1993;7:155e160. https://doi.org/10.1096/fasebj.7.1.7678559.

[182]

Patop IL, Wüst S, Kadener S. Past, present and future of circRNAs. EMBO J. 2019;38:e100836. https://doi.org/10.15252/embj.2018100836.

[183]

Suzuki H, Tsukahara T. A view of pre-mRNA splicing from RNase R resistant RNAs. Int J Mol Sci. 2014;15:9331-9342. https://doi.org/10.3390/ijms15069331.

[184]

Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019;20:675-691. https://doi.org/10.1038/s41576-019-0158-7.

[185]

Liang D, Wilusz JE. Short intronic repeat sequences facilitate circular RNA production. Genes Dev. 2014;28:2233-2247. https://doi.org/10.1101/gad.251926.114.

[186]

Wilusz JE. A 360° view of circular RNAs: from biogenesis to functions. Wiley Interdiscip Rev RNA. 2018;9:e1478. https://doi.org/10.1002/wrna.1478.

[187]

Boeckel JN, Jaé N, Heumüller AW, et al. Identiﬁcation and characterization of hypoxia-regulated endothelial circular RNA. Circ Res. 2015;117:884-890. https://doi.org/10.1161/circresaha.115.306319.

[188]

Dou X, Feng L, Ying N, et al. RNA sequencing reveals a comprehensive circular RNA expression proﬁle in a mouse model of alcoholic liver disease. Alcohol Clin Exp Res. 2020;44:415-422. https://doi.org/10.1111/acer.14265.

[189]

Meng H, Wang L, You H, Huang C, Li J. Circular RNA expression proﬁle of liver tissues in an EtOH-induced mouse model of alcoholic hepatitis. Eur J Phar-macol. 2019;862:172642. https://doi.org/10.1016/j.ejphar.2019.172642.

[190]

Salzman J, Gawad C, Wang PL, Lacayo N, Brown PO. Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One. 2012;7:e30733. https://doi.org/10.1371/journal.pone.0030733.

[191]

Verduci L, Strano S, Yarden Y, Blandino G. The circRNA-microRNA code: emerging implications for cancer diagnosis and treatment. Mol Oncol. 2019;13:669e680. https://doi.org/10.1002/1878-0261.12468.

[192]

Kularatne RN, Crist RM, Stern ST. The future of tissue-targeted lipid nanoparticle-mediated nucleic acid delivery. Pharmaceuticals (Basel). 2022;15:897. https://doi.org/10.3390/ph15070897.

[193]

Kim M, Jeong M, Hur S, et al. Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver. Sci Adv. 2021;7:eabf4398. https://doi.org/10.1126/sciadv.abf4398.

[194]

Toden S, Zumwalt TJ, Goel A. Non-coding RNAs and potential therapeutic targeting in cancer. Biochim Biophys Acta Rev Cancer. 2021;1875:188491. https://doi.org/10.1016/j.bbcan.2020.188491.

[195]

Uppaluri KR, Challa HJ, Gaur A, et al. Unlocking the potential of non-coding RNAs in cancer research and therapy. Transl Oncol. 2023;35:101730. https://doi.org/10.1016/j.tranon.2023.101730.

[196]

European Association for the Study of the Liver. EASL clinical practice guidelines: management of alcohol-related liver disease. J Hepatol. 2018;69: 154-181. https://doi.org/10.1016/j.jhep.2018.03.018.