Abstract: Interferon regulatory factor 1 (IRF-1) is a member of the IRF family. It is the first transcription factor to be identified that could bind to the interferon-stimulated response element (ISRE) on the target gene and displays crucial roles in the interferon-induced signals and pathways. IRF-1, as an important medium, has all of the advantages of full cell cycle regulation, cell death signaling transduction, and reinforcing immune surveillance, which are well documented. Current studies indicate that IRF-1 is of vital importance to the occurrence and evolution of multifarious liver diseases, including but not limited to inhibiting the replication of the hepatitis virus (A/B/C/E), alleviating the progression of liver fibrosis, and aggravating hepatic ischemia-reperfusion injury (HIRI). The tumor suppression of IRF-1 is related to the clinical characteristics of liver cancer patients, which makes it a potential indicator for predicting the prognosis and recurrence of liver cancer; additionally, the latest studies have revealed other effects of IRF-1 such as protection against alcoholic/non-alcoholic fatty liver disease (AFLD/NAFLD), cholangiocarcinoma suppression, and uncommon traits in other liver diseases that had previously received little attention. Intriguingly, several compounds and drugs have featured a protective function in specific liver disease models in which there is significant involvement of the IRF-1 signal. In this paper, we hope to propose a prospective research basis upon which to help decipher translational medicine applications of IRF-1 in liver disease treatment.

IRF-1在肝脏疾病调控中的关键作用：进展与展望

[1]AlcantaraFF, TangH, McLachlanA, 2002. Functional characterization of the interferon regulatory element in the enhancer 1 region of the hepatitis B virus genome. Nucleic Acids Res, 30(9):2068-2075.

[2]AlhetheelA, AlbarragA, HakamiA, et al., 2020. In the peripheral blood mononuclear cells (PBMCs) of HCV infected patients the expression of STAT1 and IRF-1 is downregulated while that of caspase-3 upregulated. Acta Virol, 64(3):352-358.

[3]ArmstrongMJ, StangMT, LiuY, et al., 2012. Interferon regulatory factor 1 (IRF-1) induces p21^WAF1/CIP1 dependent cell cycle arrest and p21^WAF1/CIP1 independent modulation of survivin in cancer cells. Cancer Lett, 319(1):56-65.

[4]AssadiaslS, ShahiA, SalehiS, et al., 2018. Interferon regulatory factors: where to stand in transplantation. Transpl Immunol, 51:76-80.

[5]BanerjeeA, MazumdarB, MeyerK, et al., 2011. Transcriptional repression of C4 complement by hepatitis C virus proteins. J Virol, 85(9):4157-4166.

[6]BenderH, WiesingerMY, NordhoffC, et al., 2009. Interleukin-27 displays interferon-γ-like functions in human hepatoma cells and hepatocytes. Hepatology, 50(2):585-591.

[7]CaiBS, DongiovanniP, CoreyKE, et al., 2020. Macrophage MerTK promotes liver fibrosis in nonalcoholic steatohepatitis. Cell Metab, 31(2):406-421.e7.

[8]CastellanetaA, YoshidaO, KimuraS, et al., 2014. Plasmacytoid dendritic cell-derived IFN-α promotes murine liver ischemia/reperfusion injury by induction of hepatocyte IRF-1. Hepatology, 60(1):267-277.

[9]CavalliM, PanG, NordH, et al., 2017. Genetic prevention of hepatitis C virus-induced liver fibrosis by allele-specific downregulation of MERTK. Hepatol Res, 47(8):826-830.

[10]ChenFF, JiangG, XuKR, et al., 2013. Function and mechanism by which interferon regulatory factor-1 inhibits oncogenesis. Oncol Lett, 5(2):417-423.

[11]ChenXY, CaiQ, LiangRK, et al., 2023. Copper homeostasis and copper-induced cell death in the pathogenesis of cardiovascular disease and therapeutic strategies. Cell Death Dis, 14(2):105.

[12]ChenYF, WangSH, ChangSJ, et al., 2014. Zhankuic acid A as a novel JAK2 inhibitor for the treatment of concanavalin A-induced hepatitis. Biochem Pharmacol, 91(2):217-230.

[13]ChenYY, SunR, JiangW, et al., 2007. Liver-specific HBsAg transgenic mice are over-sensitive to Poly(I:C)-induced liver injury in NK cell- and IFN-γ-dependent manner. J Hepatol, 47(2):183-190.

[14]ChengLP, GengL, DaiBH, et al., 2018. Repression of let-7a cluster prevents adhesion of colorectal cancer cells by enforcing a mesenchymal phenotype in presence of liver inflammation. Cell Death Dis, 9(5):489.

[15]ChoHI, KimKM, KwakJH, et al., 2013. Protective mech

[16]anism of anethole on hepatic ischemia/reperfusion injury in mice. J Nat Prod, 76(9):1717-1723.

[17]ColpittsCC, RidewoodS, SchneidermanB, et al., 2020. Hepatitis C virus exploits cyclophilin A to evade PKR. eLife, 9:e52237.

[18]CordobaSP, WangCM, WilliamsR, et al., 2006. Gene array analysis of a rat model of liver transplant tolerance identifies increased complement C3 and the STAT-1/IRF-1 pathway during tolerance induction. Liver Transpl, 12(4):636-643.

[19]CuiX, ZhaoHY, WeiS, et al., 2023. Hepatocellular carcinoma-derived FOXO1 inhibits tumor progression by suppressing IL-6 secretion from macrophages. Neoplasia, 40:100900.

[20]CuiZL, LiSP, LiuZR, et al., 2018. Interferon regulatory factor 1 activates autophagy to aggravate hepatic ischemia-reperfusion injury by increasing high mobility group box 1 release. Cell Physiol Biochem, 48(1):328-338.

[21]DevarbhaviH, AsraniSK, ArabJP, et al., 2023. Global burden of liver disease: 2023 update. J Hepatol, 79(2):516-537.

[22]DhuparR, KluneJR, EvankovichJ, et al., 2011. Interferon regulatory factor 1 mediates acetylation and release of high mobility group box 1 from hepatocytes during murine liver ischemia-reperfusion injury. Shock, 35(3):293-301.

[23]DongK, DuQ, CuiX, et al., 2020. MicroRNA-301a (miR-301a) is induced in hepatocellular carcinoma (HCC) and down-regulates the expression of interferon regulatory factor-1. Biochem Biophys Res Commun, 524(2):273-279.

[24]DuQ, LuoJ, YangMQ, et al., 2020. iNOS/NO is required for IRF1 activation in response to liver ischemia-reperfusion in mice. Mol Med, 26:56.

[25]EbineK, KumarK, PhamTN, et al., 2018. Interplay between interferon regulatory factor 1 and BRD4 in the regulation of PD-L1 in pancreatic stellate cells. Sci Rep, 8:13225.

[26]EisensteinM, 2023. Seven technologies to watch in 2023. Nature, 613(7945):794-797.

[27]EricksonL, CrewsG, PanF, et al., 2004. Unique gene expression profiles of heart allograft rejection in the interferon regulatory factor-1-deficient mouse. Transpl Immunol, 13(3):169-175.

[28]FujitaT, ReisLF, WatanabeN, et al., 1989. Induction of the transcription factor IRF-1 and interferon-beta mRNAs by cytokines and activators of second-messenger pathways. Proc Natl Acad Sci USA, 86(24):9936-9940.

[29]GabrielliF, AlbertiF, RussoC, et al., 2023. Treatment options for hepatitis A and E: a non-systematic review. Viruses, 15(5):1080.

[30]GoonetillekeM, KukN, CorreiaJ, et al., 2021. Addressing the liver progenitor cell response and hepatic oxidative stress in experimental non-alcoholic fatty liver disease/non-alcoholic steatohepatitis using amniotic epithelial cells. Stem Cell Res Ther, 12:429.

[31]GuJJ, DengCC, FengQL, et al., 2023. Relief of extracellular matrix deposition repression by downregulation of IRF1-mediated TWEAK/Fn14 signaling in keloids. J Invest Dermatol, 143(7):1208-1219.e6.

[32]GuidottiLG, MorrisA, MendezH, et al., 2002. Interferon-regulated pathways that control hepatitis B virus replication in transgenic mice. J Virol, 76(6):2617-2621.

[33]GuoJY, HanST, ChenQ, et al., 2023. Analysis of potential immune-related genes involved in the pathogenesis of ischemia-reperfusion injury following liver transplantation. Front Immunol, 14:1126497.

[34]GuoY, LuanLM, PatilNK, et al., 2017. Immunobiology of the IL-15/IL-15Rα complex as an antitumor and antiviral agent. Cytokine Growth Factor Rev, 38:10-21.

[35]GuoYN, LuH, XuL, et al., 2019. The response of hepatitis B virus genotype to interferon is associated with a mutation in the interferon-stimulated response element. Medicine (Baltimore), 98(51):e18442.

[36]HajikhezriZ, RoohvandF, MalekiM, et al., 2021. HCV core/NS3 protein immunization with “N-terminal heat shock gp96 protein (rNT (gp96))” induced strong and sustained Th1-type cytokines in immunized mice. Vaccines (Basel), 9(3):215.

[37]HamaN, YanagisawaY, DonoK, et al., 2009. Gene expression profiling of acute cellular rejection in rat liver transplantation using DNA microarrays. Liver Transpl, 15(5):509-521.

[38]HaradaH, TakahashiEI, ItohS, et al., 1994. Structure and regulation of the human interferon regulatory factor 1 (IRF-1) and IRF-2 genes: implications for a gene network in the interferon system. Mol Cell Biol, 14(2):1500-1509.

[39]Hojo-SouzaNS, de AzevedoPO, de CastroJT, et al., 2020. Contributions of IFN-γ and granulysin to the clearance of Plasmodium yoelii blood stage. PLoS Pathog, 16(9):e1008840.

[40]ItsuiY, SakamotoN, KurosakiM, et al., 2006. Expressional screening of interferon-stimulated genes for antiviral activity against hepatitis C virus replication. J Viral Hepat, 13(10):690-700.

[41]JanfeshanS, YaghobiR, EidiA, et al., 2017. Expression profile of interferon regulatory factor 1 in chronic hepatitis B virus-infected liver transplant patients. Exp Clin Transplant, 15(6):669-675.

[42]JengWJ, PapatheodoridisGV, LokASF, 2023. Hepatitis B. Lancet, 401(10381):1039-1052.

[43]JeongWI, ParkO, RadaevaS, et al., 2006. STAT1 inhibits liver fibrosis in mice by inhibiting stellate cell proliferation and stimulating NK cell cytotoxicity. Hepatology, 44(6):1441-1451.

[44]JiangWL, ChenGX, PuJ, 2022. The transcription factor interferon regulatory factor-1 is an endogenous mediator of myocardial ischemia reperfusion injury. Cell Biol Int, 46(1):63-72.

[45]JungCR, ChoiS, ImDS, 2007. The NS5A protein of hepatitis C virus represses gene expression of hRPB10α, a common subunit of host RNA polymerases, through interferon regulatory factor-1 binding site. Virus Res, 129(2):155-165.

[46]KanazawaN, KurosakiM, SakamotoN, et al., 2004. Regulation of hepatitis C virus replication by interferon regulatory factor 1. J Virol, 78(18):9713-9720.

[47]KielarML, JeyarajahDR, PenfieldJG, et al., 2000. Docosahexaenoic acid decreases IRF-1 mRNA and thus inhibits activation of both the IRF-E and NFκd response elements of the iNOS promoter. Transplantation, 69(10):2131-2137.

[48]KimGW, ImamH, KhanM, et al., 2021. HBV-induced increased N6 methyladenosine modification of PTEN RNA affects innate immunity and contributes to HCC. Hepatology, 73(2):533-547.

[49]KimH, MazumdarB, BoseSK, et al., 2012. Hepatitis C virus-mediated inhibition of cathepsin S increases invariant-chain expression on hepatocyte surface. J Virol, 86(18):9919-9928.

[50]KimKH, DhuparR, UekiS, et al., 2009. Donor graft interferon regulatory factor-1 gene transfer worsens liver transplant ischemia/reperfusion injury. Surgery, 146(2):181-189.

[51]KisselevaT, BrennerD, 2021. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol, 18(3):151-166.

[52]KluneJR, BartelsC, LuoJ, et al., 2018. IL-23 mediates murine liver transplantation ischemia-reperfusion injury via IFN-γ/IRF-1 pathway. Am J Physiol Gastrointest Liver Physiol, 315(6):G991-G1002.

[53]KomollRM, HuQL, OlarewajuO, et al., 2021. MicroRNA-342-3p is a potent tumour suppressor in hepatocellular carcinoma. J Hepatol, 74(1):122-134.

[54]KorachiM, CeranN, AdaletiR, et al., 2013. An association study of functional polymorphic genes IRF-1, IFNGR-1, and IFN-γ with disease progression, aminotransferaseaspartate, aminotransferasealanine, and viral load in chronic hepatitis B and C. Int J Infect Dis, 17(1):e44-e49.

[55]KuramitsuK, SverdlovDY, LiuSB, et al., 2013. Failure of fibrotic liver regeneration in mice is linked to a severe fibrogenic response driven by hepatic progenitor cell activation. Am J Pathol, 183(1):182-194.

[56]LangZC, YuSH, HuYH, et al., 2023. Ginsenoside Rh2 promotes hepatic stellate cell ferroptosis and inactivation via regulation of IRF1-inhibited SLC7A11. Phytomedicine, 118:154950.

[57]LeeSH, KimJW, LeeHW, et al., 2003. Interferon regulatory factor-1 (IRF-1) is a mediator for interferon-γ induced attenuation of telomerase activity and human telomerase reverse transcriptase (hTERT) expression. Oncogene, 22(3):381-391.

[58]LeiL, BruneauA, el MourabitH, et al., 2022. Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis. Hepatology, 76(5):1360-1375.

[59]LiHD, ChenX, XuJJ, et al., 2024. GRP/GRPR enhances alcohol-associated liver injury via the IRF1-mediated Caspase-1 inflammasome and NOX2-dependent ROS pathway. Hepatology, 79(2):392-408.

[60]LiK, FengZJ, WangLS, et al., 2023. Chlorogenic acid alleviates hepatic ischemia-reperfusion injury by inhibiting oxidative stress, inflammation, and mitochondria-mediated apoptosis in vivo and in vitro. Inflammation, 46(3):1061-1076.

[61]LiPY, DuQ, CaoZX, et al., 2012. Interferon-gamma induces autophagy with growth inhibition and cell death in human hepatocellular carcinoma (HCC) cells through interferon-regulatory factor-1 (IRF-1). Cancer Lett, 314(2):213-222.

[62]LiSP, ZhangJJ, WangZ, et al., 2016. MicroRNA-17 regulates autophagy to promote hepatic ischemia/reperfusion injury via suppression of signal transductions and activation of transcription-3 expression. Liver Transpl, 22(12):1697-1709.

[63]LiSP, HeJD, XuHW, et al., 2021. Autophagic activation of IRF-1 aggravates hepatic ischemia-reperfusion injury via JNK signaling. MedComm, 2(1):91-100.

[64]LiXC, HuangJQ, WuQL, et al., 2023. Inhibition of checkpoint kinase 1 (CHK1) upregulates interferon regulatory factor 1 (IRF1) to promote apoptosis and activate anti-tumor immunity via MICA in hepatocellular carcinoma (HCC). Cancers (Basel), 15(3):850.

[65]LiY, WuY, ZhengXH, et al., 2016. Cytoplasm-translocated Ku70/80 complex sensing of HBV DNA induces hepatitis-associated chemokine secretion. Front Immunol, 7:569.

[66]LiangS, ZhongZY, KimSY, et al., 2019. Murine macrophage autophagy protects against alcohol-induced liver injury by degrading interferon regulatory factor 1 (IRF1) and removing damaged mitochondria. J Biol Chem, 294(33):12359-12369.

[67]LinYH, WuMH, LiaoCJ, et al., 2015. Repression of microRNA-130b by thyroid hormone enhances cell motility. J Hepatol, 62(6):1328-1340.

[68]LiuFH, NiWJ, ZhangJJ, et al., 2017. Administration of curcumin protects kidney tubules against renal ischemia-reperfusion injury (RIRI) by modulating nitric oxide (NO) signaling pathway. Cell Physiol Biochem, 44(1):401-411.

[69]LiuK, LeeJ, OuJHJ, 2018. Autophagy and mitophagy in hepatocarcinogenesis. Mol Cell Oncol, 5(2):e1405142.

[70]LiuX, XuJ, RosenthalS, et al., 2020. Identification of lineage-specific transcription factors that prevent activation of hepatic stellate cells and promote fibrosis resolution. Gastroenterology, 158(6):1728-1744.e14.

[71]LuC, PengK, GuoH, et al., 2018. miR-18a-5p promotes cell invasion and migration of osteosarcoma by directly targeting IRF2. Oncol Lett, 16(3):3150-3156.

[72]MathewR, WhiteE, 2011. Autophagy in tumorigenesis and energy metabolism: friend by day, foe by night. Curr Opin Genet Dev, 21(1):113-119.

[73]MiyazakiM, OhashiR, TsujiT, et al., 1998. Transforming growth factor-β1 stimulates or inhibits cell growth via down- or up-regulation of p21/Waf1. Biochem Biophys Res Commun, 246(3):873-880.

[74]MiyazakiM, SakaguchiM, AkiyamaI, et al., 2004. Involvement of interferon regulatory factor 1 and S100C/A11 in growth inhibition by transforming growth factor β1 in human hepatocellular carcinoma cells. Cancer Res, 64(12):4155-4161.

[75]MongaSP, 2018. Lipid metabolic reprogramming in hepatic ischemia-reperfusion injury. Nat Med, 24(1):6-7.

[76]MoriyamaY, NishiguchiS, TamoriA, et al., 2001. Tumor-suppressor effect of interferon regulatory factor-1 in human hepatocellular carcinoma. Clin Cancer Res, 7(5):1293-1298.

[77]MoroA, SantosA, ArañaMJ, et al., 2000. Activation of the human p27^Kip1 promoter by IFNα 2b. Biochem Biophys Res Commun, 269(1):31-34.

[78]NabavizadehSH, JanfeshanS, KarimiMH, et al., 2018. Association between IRF1 gene expression and liver enzymes in HBV-infected liver transplant recipients with and without experience of rejection. Int J Organ Transplant Med, 9(2):68-74

[79]NakamuraK, KageyamaS, Kupiec-WeglinskiJW, 2019. The evolving role of neutrophils in liver transplant ischemia-reperfusion injury. Curr Transplant Rep, 6(1):78-89.

[80]NakaoK, NakataK, YamashitaM, et al., 1999. p48 (ISGF-3γ) is involved in interferon-α-induced suppression of hepatitis B virus enhancer-1 activity. J Biol Chem, 274(40):28075-28078.

[81]NandakumarR, FinsterbuschK, LippsC, et al., 2013. Hepatitis C virus replication in mouse cells is restricted by IFN-dependent and -independent mechanisms. Gastroenterology, 145(6):1414-1423.e1.

[82]NiDL, WeiH, ChenWY, et al., 2019. Ceria nanoparticles meet hepatic ischemia-reperfusion injury: the perfect imperfection. Adv Mater, 31(40):1902956.

[83]NiYA, ChenH, NieH, et al., 2021. HMGB1: an overview of its roles in the pathogenesis of liver disease. J Leukoc Biol, 110(5):987-998.

[84]OhJE, ShimKY, LeeJI, et al., 2017. 1-Methyl-L-tryptophan promotes the apoptosis of hepatic stellate cells arrested by interferon-γ by increasing the expression of IFN-γRβ, IRF-1 and FAS. Int J Mol Med, 40(2):576-582.

[85]PanS, LiuX, MaYJ, et al., 2018. Herpes simplex virus 1 γ₁34.5 protein inhibits STING activation that restricts viral replication. J Virol, 92(20):e01015-18.

[86]PangXL, WangZX, ZhaiNC, et al., 2016. IL-10 plays a central regulatory role in the cytokines induced by hepatitis C virus core protein and polyinosinic acid: polycytodylic acid. Int Immunopharmacol, 38:284-290.

[87]PettaS, ValentiL, MarraF, et al., 2016. MERTK rs4374383 polymorphism affects the severity of fibrosis in non-alcoholic fatty liver disease. J Hepatol, 64(3):682-690.

[88]The Polaris Observatory HCV Collaborators, 2022. Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study. Lancet Gastroenterol Hepatol, 7(5):396-415.

[89]QiaoYL, ZhangXL, ZhaoGM, et al., 2019. Hepatocellular iNOS protects liver from ischemia/reperfusion injury through HSF1-dependent activation of HSP70. Biochem Biophys Res Commun, 512(4):882-888.

[90]QiaoYL, XiaoF, LiWK, et al., 2020. Hepatocellular HO-1 mediated iNOS-induced hepatoprotection against liver ischemia reperfusion injury. Biochem Biophys Res Commun, 521(4):1095-1100.

[91]RaniR, KumarS, SharmaA, et al., 2018. Mechanisms of concanavalin A-induced cytokine synthesis by hepatic stellate cells: distinct roles of interferon regulatory factor-1 in liver injury. J Biol Chem, 293(48):18466-18476.

[92]RosainJ, NeehusAL, ManryJ, et al., 2023. Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria. Cell, 186(3):621-645.e33.

[93]RueschenbaumS, CaiCC, SchmidtM, et al., 2021. Translation of IRF-1 restricts hepatic interleukin-7 production to types I and II interferons: implications for hepatic immunity. Front Immunol, 11:581352.

[94]SaitoH, TadaS, NakamotoN, et al., 2005. Contribution of Irf-1 promoter polymorphisms to the Th1-type cell response and interferon-β monotherapy for chronic hepatitis C. Hepatol Res, 32(1):25-32.

[95]ShiH, GuanSH, 2009. Increased apoptosis in HepG2.2.15 cells with hepatitis B virus expression by synergistic induction of interferon-γ and tumour necrosis factor-α. Liver Int, 29(3):349-355.

[96]SolomonM, Flodström-TullbergM, SarvetnickN, 2011. Beta-cell specific expression of suppressor of cytokine signaling-1 (SOCS-1) delays islet allograft rejection by down-regulating Interferon Regulatory Factor-1 (IRF-1) signaling. Transpl Immunol, 24(3):181-188.

[97]SorrentinoC, D'AntonioL, FieniC, et al., 2021. Colorectal cancer-associated immune exhaustion involves T and B lymphocytes and conventional NK cells and correlates with a shorter overall survival. Front Immunol, 12:778329.

[98]SoyozM, PehlivanM, TatarE, et al., 2021. Consideration of IL-2, IFN-γ and IL-4 expression and methylation levels in CD4+ T cells as a predictor of rejection in kidney transplant. Transpl Immunol, 68:101414.

[99]SunB, ZhouYM, FangYT, et al., 2019. Colorectal cancer exosomes induce lymphatic network remodeling in lymph nodes. Int J Cancer, 145(6):1648-1659.

[100]SyBT, HoanNX, TongHV, et al., 2018. Genetic variants of interferon regulatory factor 5 associated with chronic hepatitis B infection. World J Gastroenterol, 24(2):248-256.

[101]TadaS, SaitoH, TsunematsuS, et al., 1998. Interferon regulatory factor-1 gene abnormality and loss of growth inhibitory effect of interferon-alpha in human hepatoma cell lines. Int J Oncol, 13(6):1207-1216.

[102]TanAT, SchreiberS, 2020. Adoptive T-cell therapy for HBV-associated HCC and HBV infection. Antiviral Res, 176:104748.

[103]TaoHS, LiL, LiaoNS, et al., 2021. Thymic epithelial cell-derived IL-15 and IL-15 receptor α chain foster local environment for type 1 innate like T cell development. Front Immunol, 12:623280.

[104]ThomasE, ChengWH, DyllaDE, et al., 2022. Awareness and epidemiology of chronic hepatitis C virus infections in florida. Infect Dis Ther, 11(1):451-462.

[105]ThygesenSJ, StaceyKJ, 2019. IRF1 and IRF2 regulate the non-canonical inflammasome. EMBO Rep, 20(9):e48891.

[106]TianXH, LiuY, LiuXL, et al., 2019. Glycyrrhizic acid ammonium salt alleviates Concanavalin A-induced immunological liver injury in mice through the regulation of the balance of immune cells and the inhibition of hepatocyte apoptosis. Biomed Pharmacother, 120:109481.

[107]TsungA, StangMT, IkedaA, et al., 2006. The transcription factor interferon regulatory factor-1 mediates liver damage during ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol, 290(6):G1261-G1268.

[108]TsungA, KluneJR, ZhangXH, et al., 2007. HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. J Exp Med, 204(12):2913-2923.

[109]UekiS, DhuparR, CardinalJ, et al., 2010. Critical role of interferon regulatory factor-1 in murine liver transplant ischemia reperfusion injury. Hepatology, 51(5):1692-1701.

[110]VillanuevaA, 2019. Hepatocellular carcinoma. N Engl J Med, 380(15):1450-1462.

[111]WanPQ, ZhangJH, DuQ, et al., 2018a. The clinical significance and biological function of interferon regulatory factor 1 in cholangiocarcinoma. Biomed Pharmacother, 97:771-777.

[112]WanPQ, ChiX, DuQ, et al., 2018b. miR-383 promotes cholangiocarcinoma cell proliferation, migration, and invasion through targeting IRF1. J Cell Biochem, 119(12):9720-9729.

[113]WanPQ, ZhangJH, DuQ, et al., 2020. Analysis of the relationship between microRNA-31 and interferon regulatory factor-1 in hepatocellular carcinoma cells. Eur Rev Med Pharmacol Sci, 24(2):647-654.

[114]WangDP, YuZX, HeZC, et al., 2020. Apolipoprotein L1 is transcriptionally regulated by SP1, IRF1 and IRF2 in hepatoma cells. FEBS Lett, 594(19):3108-3121.

[115]WangJJ, LiHY, XueBB, et al., 2020. IRF1 promotes the innate immune response to viral infection by enhancing the activation of IRF3. J Virol, 94(22):e01231-20.

[116]WangMH, YinHL, XiaY, et al., 2021. Huganbuzure granule attenuates concanavalin-A-induced immune liver injury in mice via regulating the balance of Th1/Th2/Th17/Treg cells and inhibiting apoptosis. Evid Based Complement Alternat Med, 2021:5578021.

[117]WangR, GuoH, TangXT, et al., 2022. Interferon gamma-induced interferon regulatory factor 1 activates transcription of HHLA2 and induces immune escape of hepatocellular carcinoma cells. Inflammation, 45(1):308-330.

[118]WangZB, PanBL, QiuJC, et al., 2023. SUMOylated IL-33 in the nucleus stabilizes the transcription factor IRF1 in hepatocellular carcinoma cells to promote immune escape. Sci Signal, 16(776):eabq3362.

[119]WengHL, FengDC, RadaevaS, et al., 2013. IFN-γ inhibits liver progenitor cell proliferation in HBV-infected patients and in 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet-fed mice. J Hepatol, 59(4):738-745.

[120]Wietzke-BraunP, MaouziAB, MänhardtLB, et al., 2006. Interferon regulatory factor-1 promoter polymorphism and the outcome of hepatitis C virus infection. Eur J Gastroenterol Hepatol, 18(9):991-997.

[121]WuHX, LiY, ShiGJ, et al., 2022. Hepatic interferon regulatory factor 8 expression suppresses hepatocellular carcinoma progression and enhances the response to anti-programmed cell death protein-1 therapy. Hepatology, 76(6):1602-1616.

[122]XiaoG, JinLL, LiuCQ, et al., 2019. EZH2 negatively regulates PD-L1 expression in hepatocellular carcinoma. J Immunother Cancer, 7(1):300.

[123]XuL, ZhouXY, WangWS, et al., 2016. IFN regulatory factor 1 restricts hepatitis E virus replication by activating STAT1 to induce antiviral IFN-stimulated genes. FASEB J, 30(10):3352-3367.

[124]XuL, WangWS, LiYL, et al., 2017. RIG-I is a key antiviral interferon-stimulated gene against hepatitis E virus regardless of interferon production. Hepatology, 65(6):1823-1839.

[125]YamaneD, FengH, Rivera-SerranoEE, et al., 2019. Basal expression of interferon regulatory factor 1 drives intrinsic hepatocyte resistance to multiple RNA viruses. Nat Microbiol, 4(7):1096-1104.

[126]YanB, LuoJ, KaltenmeierC, et al., 2020. Interferon Regulatory Factor-1 (IRF1) activates autophagy to promote liver ischemia/reperfusion injury by inhibiting β-catenin in mice. PLoS ONE, 15(11):e0239119.

[127]YanYH, LiangZH, DuQ, et al., 2016. MicroRNA-23a downregulates the expression of interferon regulatory factor-1 in hepatocellular carcinoma cells. Oncol Rep, 36(2):633-640.

[128]YanYH, ZhengLT, DuQ, et al., 2020. Interferon regulatory factor 1 (IRF-1) and IRF-2 regulate PD-L1 expression in hepatocellular carcinoma (HCC) cells. Cancer Immunol Immunother, 69(9):1891-1903.

[129]YanYH, ZhengLT, DuQ, et al., 2021a. Interferon regulatory factor 1 (IRF-1) activates anti-tumor immunity via CXCL10/CXCR3 axis in hepatocellular carcinoma (HCC). Cancer Lett, 506:95-106.

[130]YanYH, ZhengLT, DuQ, et al., 2021b. Interferon regulatory factor 1 (IRF-1) downregulates Checkpoint kinase 1 (CHK1) through miR-195 to upregulate apoptosis and PD-L1 expression in Hepatocellular carcinoma (HCC) cells. Br J Cancer, 125(1):101-111.

[131]YanaiH, NegishiH, TaniguchiT, 2012. The IRF family of transcription factors: inception, impact and implications in oncogenesis. Oncoimmunology, 1(8):1376-1386.

[132]YangMQ, DuQ, GoswamiJ, et al., 2018. Interferon regulatory factor 1-Rab27a regulated extracellular vesicles promote liver ischemia/reperfusion injury. Hepatology, 67(3):1056-1070.

[133]YanoH, IemuraA, HaramakiM, et al., 1999. Interferon alfa receptor expression and growth inhibition by interferon alfa in human liver cancer cell lines. Hepatology, 29(6):1708-1717.

[134]YokotaS, YoshidaO, DouL, et al., 2015. IRF-1 promotes liver transplant ischemia/reperfusion injury via hepatocyte IL-15/IL-15Rα production. J Immunol, 194(12): 6045-6056.

[135]YuM, XueHZ, WangYD, et al., 2017. miR-345 inhibits tumor metastasis and EMT by targeting IRF1-mediated mTOR/STAT3/AKT pathway in hepatocellular carcinoma. Int J Oncol, 50(3):975-983.

[136]YuWW, HeJB, WangF, et al., 2023. NR4A1 mediates NK-cell dysfunction in hepatocellular carcinoma via the IFN-γ/p-STAT1/IRF1 pathway. Immunology, 169(1):69-82.

[137]ZekriARN, RANMoharram, MohamedWS, et al., 2010. Disease progression from chronic hepatitis C to cirrhosis and hepatocellular carcinoma is associated with repression of interferon regulatory factor-1. Eur J Gastroenterol Hepatol, 22(4):450-456.

[138]ZenkeK, MuroiM, TanamotoKI, 2018. IRF1 supports DNA binding of STAT1 by promoting its phosphorylation. Immunol Cell Biol, 96(10):1095-1103.

[139]ZhangHM, LiSP, YuY, et al., 2016. Bi-directional roles of IRF-1 on autophagy diminish its prognostic value as compared with Ki67 in liver transplantation for hepatocellular carcinoma. Oncotarget, 7(25):37979-37992.

[140]ZhangL, SongYL, ChenL, et al., 2020. MiR-20a-containing exosomes from umbilical cord mesenchymal stem cells alleviates liver ischemia/reperfusion injury. J Cell Physiol, 235(4):3698-3710.

[141]ZhangLM, ChengTL, YangH, et al., 2022. Interferon regulatory factor-1 regulates cisplatin-induced apoptosis and autophagy in A549 lung cancer cells. Med Oncol, 39(4):38.

[142]ZhangMQ, ZhaoQ, ZhangJP, 2020. A new transcription factor ATG10S activates IFNL2 transcription by binding at an IRF1 site in HepG2 cells. Autophagy, 16(12):2167-2179.

[143]ZhangY, ZhangJJ, FengDY, et al., 2022. IRF1/ZNF350/GPX4-mediated ferroptosis of renal tubular epithelial cells promote chronic renal allograft interstitial fibrosis. Free Radic Biol Med, 193:579-594.

[144]ZhangYC, ZhangYL, WangJ, et al., 2020. Amarogentin inhibits liver cancer cell angiogenesis after insufficient radiofrequency ablation via affecting stemness and the p53-dependent VEGFA/Dll4/Notch1 pathway. Biomed Res Int, 2020:5391058.

[145]ZhouH, TangYD, ZhengCF, 2022. Revisiting IRF1-mediated antiviral innate immunity. Cytokine Growth Factor Rev, 64:1-6.

[146]ZhouR, TangW, RenYX, et al., 2006. Preventive effects of (5R)-5-hydroxytriptolide on concanavalin A-induced hepatitis. Eur J Pharmacol, 537(1-3):181-189.

[147]ZhuRX, ChengASL, ChanHLY, et al., 2019. Growth arrest-specific gene 2 suppresses hepatocarcinogenesis by intervention of cell cycle and p53-dependent apoptosis. World J Gastroenterol, 25(32):4715-4726.

[148]ZhuSF, YuanW, DuYL, et al., 2023. Research progress of lncRNA and miRNA in hepatic ischemia-reperfusion injury. Hepatobiliary Pancreat Dis Int, 22(1):45-53.

[149]ZuoHW, WangYX, YuanMS, et al., 2023. Small extracellular vesicles from HO-1-modified bone marrow-derived mesenchymal stem cells attenuate ischemia-reperfusion injury after steatotic liver transplantation by suppressing ferroptosis via miR-214-3p. Cell Signal, 109:110793.