{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:45:27Z","timestamp":1785422727773,"version":"3.56.0"},"reference-count":170,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development, and Innovations of the Republic of Serbia","award":["451-03-47\/2023-01\/200017"],"award-info":[{"award-number":["451-03-47\/2023-01\/200017"]}]},{"name":"Ministry of Science, Technological Development, and Innovations of the Republic of Serbia","award":["0802303"],"award-info":[{"award-number":["0802303"]}]},{"name":"Research Theme \u201cMolecular alterations as prognostic and predictive markers in human malignant tumours\u201d","award":["451-03-47\/2023-01\/200017"],"award-info":[{"award-number":["451-03-47\/2023-01\/200017"]}]},{"name":"Research Theme \u201cMolecular alterations as prognostic and predictive markers in human malignant tumours\u201d","award":["0802303"],"award-info":[{"award-number":["0802303"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is one of the most frequent cancers in humans, characterised by a high resistance to conventional chemotherapy, late diagnosis, and a high mortality rate. It is necessary to elucidate the molecular mechanisms involved in hepatocarcinogenesis to improve diagnosis and treatment outcomes. The Runt-related (RUNX) family of transcription factors (RUNX1, RUNX2, and RUNX3) participates in cardinal biological processes and plays paramount roles in the pathogenesis of numerous human malignancies. Their role is often controversial as they can act as oncogenes or tumour suppressors and depends on cellular context. Evidence shows that deregulated RUNX genes may be involved in hepatocarcinogenesis from the earliest to the latest stages. In this review, we summarise the topical evidence on the roles of RUNX gene family members in HCC. We discuss their possible application as non-invasive molecular markers for early diagnosis, prognosis, and development of novel treatment strategies in HCC patients.<\/jats:p>","DOI":"10.3390\/cells12182303","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T02:26:17Z","timestamp":1695090377000},"page":"2303","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Multiple Roles of the RUNX Gene Family in Hepatocellular Carcinoma and Their Potential Clinical Implications"],"prefix":"10.3390","volume":"12","author":[{"given":"Milena","family":"Krajnovi\u0107","sequence":"first","affiliation":[{"name":"Laboratory for Radiobiology and Molecular Genetics, Vin\u010da Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovi\u0107a Alasa 12-14, Vin\u010da, 11351 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2983-4151","authenticated-orcid":false,"given":"Bojana","family":"Ko\u017eik","sequence":"additional","affiliation":[{"name":"Laboratory for Radiobiology and Molecular Genetics, Vin\u010da Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovi\u0107a Alasa 12-14, Vin\u010da, 11351 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6487-6365","authenticated-orcid":false,"given":"Ana","family":"Bo\u017eovi\u0107","sequence":"additional","affiliation":[{"name":"Laboratory for Radiobiology and Molecular Genetics, Vin\u010da Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovi\u0107a Alasa 12-14, Vin\u010da, 11351 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sne\u017eana","family":"Jovanovi\u0107-\u0106upi\u0107","sequence":"additional","affiliation":[{"name":"Laboratory for Radiobiology and Molecular Genetics, Vin\u010da Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovi\u0107a Alasa 12-14, Vin\u010da, 11351 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"key":"ref_1","unstructured":"Asafo-Agyei, K.O., and Samant, H. (2023). StatPearls, StatPearls Publishing."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular Carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.2147\/JHC.S61146","article-title":"Hepatocellular Carcinoma: A Review","volume":"3","author":"Balogh","year":"2016","journal-title":"J. Hepatocell. Carcinoma"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.currproblcancer.2017.10.007","article-title":"Hepatocellular Carcinoma in the Era of Immunotherapy","volume":"42","author":"Sim","year":"2018","journal-title":"Curr. Probl. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Suresh, D., Srinivas, A.N., Prashant, A., Harikumar, K.B., and Kumar, D.P. (2023). Therapeutic Options in Hepatocellular Carcinoma: A Comprehensive Review. Clin. Exp. Med.","DOI":"10.1007\/s10238-023-01014-3"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1002\/ijc.27964","article-title":"RUNX Family: Regulation and Diversification of Roles through Interacting Proteins","volume":"132","author":"Chuang","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_7","first-page":"3","article-title":"RUNX Family: Oncogenes or Tumor Suppressors (Review)","volume":"42","author":"Rojas","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nrc3877","article-title":"The RUNX Family: Developmental Regulators in Cancer","volume":"15","author":"Ito","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4211","DOI":"10.1038\/sj.onc.1207670","article-title":"Structure and Regulated Expression of Mammalian RUNX Genes","volume":"23","author":"Levanon","year":"2004","journal-title":"Oncogene"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yi, H., He, Y., Zhu, Q., and Fang, L. (2022). RUNX Proteins as Epigenetic Modulators in Cancer. Cells, 11.","DOI":"10.3390\/cells11223687"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"dev148296","DOI":"10.1242\/dev.148296","article-title":"RUNX Transcription Factors: Orchestrators of Development","volume":"146","author":"Mevel","year":"2019","journal-title":"Development"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/nrc906","article-title":"Transcription Factors as Targets for Cancer Therapy","volume":"2","author":"Darnell","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1182\/blood-2016-10-687830","article-title":"Role of RUNX1 in Hematological Malignancies","volume":"129","author":"Sood","year":"2017","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4198","DOI":"10.1038\/sj.onc.1207755","article-title":"Oncogenic Potential of the RUNX Gene Family: \u2018Overview\u2019","volume":"23","author":"Ito","year":"2004","journal-title":"Oncogene"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lee, Y.M. (2022). RUNX Family in Hypoxic Microenvironment and Angiogenesis in Cancers. Cells, 11.","DOI":"10.3390\/cells11193098"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1532\/IJH97.05075","article-title":"Runx1\/AML1 in Normal and Abnormal Hematopoiesis","volume":"82","author":"Yamagata","year":"2005","journal-title":"Int. J. Hematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/s12015-011-9337-4","article-title":"Transcription Factor Runx2 and Its Application to Bone Tissue Engineering","volume":"8","author":"Innamorati","year":"2012","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/s00418-013-1077-x","article-title":"Abnormal Liver Differentiation and Excessive Angiogenesis in Mice Lacking Runx3","volume":"139","author":"Lee","year":"2013","journal-title":"Histochem. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/978-981-10-3233-2_8","article-title":"Roles of Runx Genes in Nervous System Development","volume":"Volume 962","author":"Groner","year":"2017","journal-title":"RUNX Proteins in Development and Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.cell.2021.12.018","article-title":"Spatial Proteogenomics Reveals Distinct and Evolutionarily Conserved Hepatic Macrophage Niches","volume":"185","author":"Guilliams","year":"2022","journal-title":"Cell"},{"key":"ref_21","unstructured":"(2023, March 11). Human All Liver Cells. Available online: https:\/\/www.livercellatlas.org\/umap-humanAll.php."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"156","DOI":"10.2478\/jtim-2022-0013","article-title":"Pan-Cancer Landscape of the RUNX Protein Family Reveals Their Potential as Carcinogenic Biomarkers and the Mechanisms Underlying Their Action","volume":"10","author":"Pan","year":"2022","journal-title":"J. Transl. Intern. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","article-title":"Genomic Classification and Prognosis in Acute Myeloid Leukemia","volume":"374","author":"Papaemmanuil","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e202000864","DOI":"10.26508\/lsa.202000864","article-title":"Different Mutant RUNX1 Oncoproteins Program Alternate Haematopoietic Differentiation Trajectories","volume":"4","author":"Kellaway","year":"2021","journal-title":"Life Sci. Alliance"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4284","DOI":"10.1038\/sj.onc.1207779","article-title":"Point Mutations in the RUNX1\/AML1 Gene: Another Actor in RUNX Leukemia","volume":"23","author":"Osato","year":"2004","journal-title":"Oncogene"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1182\/blood-2016-08-733196","article-title":"Diagnosis and Management of AML in Adults: 2017 ELN Recommendations from an International Expert Panel","volume":"129","author":"Estey","year":"2017","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1038\/leu.2016.126","article-title":"RUNX1 Mutations in Acute Myeloid Leukemia Are Associated with Distinct Clinico-Pathologic and Genetic Features","volume":"30","author":"Gaidzik","year":"2016","journal-title":"Leukemia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.1182\/blood.V85.12.3662.bloodjournal85123662","article-title":"The t(12;21) of Acute Lymphoblastic Leukemia Results in a Tel-AML1 Gene Fusion","volume":"85","author":"Romana","year":"1995","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1002\/j.1460-2075.1993.tb05933.x","article-title":"The t(8;21) Translocation in Acute Myeloid Leukemia Results in Production of an AML1-MTG8 Fusion Transcript","volume":"12","author":"Miyoshi","year":"1993","journal-title":"EMBO J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1002\/j.1460-2075.1994.tb06288.x","article-title":"Generation of the AML1-EVI-1 Fusion Gene in the t(3;21)(Q26;Q22) Causes Blastic Crisis in Chronic Myelocytic Leukemia","volume":"13","author":"Mitani","year":"1994","journal-title":"EMBO J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"972","DOI":"10.4161\/cc.23963","article-title":"The RUNX1 Transcription Factor Is Expressed in Serous Epithelial Ovarian Carcinoma and Contributes to Cell Proliferation, Migration and Invasion","volume":"12","author":"Keita","year":"2013","journal-title":"Cell Cycle"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1007\/s12253-019-00694-1","article-title":"Upregulation of RUNX1 Suppresses Proliferation and Migration through Repressing VEGFA Expression in Hepatocellular Carcinoma","volume":"26","author":"Liu","year":"2020","journal-title":"Pathol. Oncol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1186\/s13046-019-1330-9","article-title":"RUNX1 Promotes Tumour Metastasis by Activating the Wnt\/\u03b2-Catenin Signalling Pathway and EMT in Colorectal Cancer","volume":"38","author":"Li","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"153142","DOI":"10.1016\/j.prp.2020.153142","article-title":"RUNX1 Regulates TGF-\u03b2 Induced Migration and EMT in Colorectal Cancer","volume":"216","author":"Lu","year":"2020","journal-title":"Pathol. Res. Pract."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1007\/s10571-016-0456-y","article-title":"RUNX1 Regulates Migration, Invasion, and Angiogenesis via P38 MAPK Pathway in Human Glioblastoma","volume":"37","author":"Sangpairoj","year":"2017","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7261","DOI":"10.1002\/jcp.29625","article-title":"RUNX1 and RUNX2 Transcription Factors Function in Opposing Roles to Regulate Breast Cancer Stem Cells","volume":"235","author":"Fritz","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lin, T.-C. (2023). RUNX2 and Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087001"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100391","DOI":"10.1016\/j.jbo.2021.100391","article-title":"Identification of GPC3 Mutation and Upregulation in a Multidrug Resistant Osteosarcoma and Its Spheroids as Therapeutic Target","volume":"30","author":"Nie","year":"2021","journal-title":"J. Bone Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5598","DOI":"10.1167\/iovs.10-6934","article-title":"Multiplex Ligation-Dependent Probe Amplification of Conjunctival Melanoma Reveals Common BRAF V600E Gene Mutation and Gene Copy Number Changes","volume":"52","author":"Lake","year":"2011","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.ccr.2013.10.003","article-title":"Runx3 Inactivation Is a Crucial Early Event in the Development of Lung Adenocarcinoma","volume":"24","author":"Lee","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0092-8674(02)00690-6","article-title":"Causal Relationship between the Loss of RUNX3 Expression and Gastric Cancer","volume":"109","author":"Li","year":"2002","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1002\/ijc.20472","article-title":"Epigenetic Inactivation OfRUNX3 in Microsatellite Unstable Sporadic Colon Cancers","volume":"112","author":"Goel","year":"2004","journal-title":"Int. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/path.1503","article-title":"Aberrant CpG Island Hypermethylation of Multiple Genes in Prostate Cancer and Prostatic Intraepithelial Neoplasia: CpG Island Methylation in Prostate Cancer and PIN","volume":"202","author":"Kang","year":"2004","journal-title":"J. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6512","DOI":"10.1158\/0008-5472.CAN-06-0369","article-title":"RUNX3 Is Frequently Inactivated by Dual Mechanisms of Protein Mislocalization and Promoter Hypermethylation in Breast Cancer","volume":"66","author":"Lau","year":"2006","journal-title":"Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Tsunematsu, T., Kudo, Y., Iizuka, S., Ogawa, I., Fujita, T., Kurihara, H., Abiko, Y., and Takata, T. (2009). RUNX3 Has an Oncogenic Role in Head and Neck Cancer. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005892"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1002\/cncr.25838","article-title":"Prognostic Significance of RUNX3 Expression in Human Melanoma: RUNX3 in Melanoma Prognosis","volume":"117","author":"Zhang","year":"2011","journal-title":"Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.ygyno.2008.09.006","article-title":"RUNX3 Protein Is Overexpressed in Human Epithelial Ovarian Cancer","volume":"112","author":"Nevadunsky","year":"2009","journal-title":"Gynecol. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9347","DOI":"10.1158\/0008-5472.CAN-05-1647","article-title":"RUNX3 Inactivation by Point Mutations and Aberrant DNA Methylation in Bladder Tumors","volume":"65","author":"Kim","year":"2005","journal-title":"Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S1535-6108(02)00049-1","article-title":"RUNX: A Trilogy of Cancer Genes","volume":"1","author":"Lund","year":"2002","journal-title":"Cancer Cell"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Nakanishi, Y., Shiraha, H., Nishina, S., Tanaka, S., Matsubara, M., Horiguchi, S., Iwamuro, M., Takaoka, N., Uemura, M., and Kuwaki, K. (2011). Loss of Runt-Related Transcription Factor 3 Expression Leads Hepatocellular Carcinoma Cells to Escape Apoptosis. BMC Cancer, 11.","DOI":"10.1186\/1471-2407-11-3"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/j.1478-3231.2005.1059.x","article-title":"Decreased Expression and Frequent Allelic Inactivation of the RUNX3 Gene at 1p36 in Human Hepatocellular Carcinoma","volume":"25","author":"Mori","year":"2005","journal-title":"Liver Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"dev146589","DOI":"10.1242\/dev.146589","article-title":"Wnt Signaling in Development and Tissue Homeostasis","volume":"145","author":"Steinhart","year":"2018","journal-title":"Development"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.ccr.2008.08.004","article-title":"RUNX3 Attenuates \u03b2-Catenin\/T Cell Factors in Intestinal Tumorigenesis","volume":"14","author":"Ito","year":"2008","journal-title":"Cancer Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/jcb.22969","article-title":"Control of RUNX3 by Histone Methyltransferases","volume":"112","author":"Lee","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/onc.2008.377","article-title":"Hypoxic Silencing of Tumor Suppressor RUNX3 by Histone Modification in Gastric Cancer Cells","volume":"28","author":"Lee","year":"2009","journal-title":"Oncogene"},{"key":"ref_56","unstructured":"(2022, August 22). cBioPortal For Cancer Genomics. Available online: https:\/\/www.cbioportal.org\/."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/13793","article-title":"Haploinsufficiency of CBFA2 Causes Familial Thrombocytopenia with Propensity to Develop Acute Myelogenous Leukaemia","volume":"23","author":"Song","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1200\/JCO.2011.40.6652","article-title":"RUNX1 Mutations Are Associated with Poor Outcome in Younger and Older Patients with Cytogenetically Normal Acute Myeloid Leukemia and with Distinct Gene and MicroRNA Expression Signatures","volume":"30","author":"Mendler","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41419-021-03617-8","article-title":"A Zic2\/Runx2\/NOLC1 Signaling Axis Mediates Tumor Growth and Metastasis in Clear Cell Renal Cell Carcinoma","volume":"12","author":"Wu","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1038\/s41418-021-00810-2","article-title":"CBF\u03b2 Promotes Colorectal Cancer Progression through Transcriptionally Activating OPN, FAM129A, and UPP1 in a RUNX2-Dependent Manner","volume":"28","author":"Wang","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"145451","DOI":"10.1016\/j.gene.2021.145451","article-title":"Cancer-Associated Fibroblasts and the Related Runt-Related Transcription Factor 2 (RUNX2) Promote Bladder Cancer Progression","volume":"775","author":"Liu","year":"2021","journal-title":"Gene"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"107383","DOI":"10.1016\/j.compbiolchem.2020.107383","article-title":"Clinical Significance of Transcription Factor RUNX2 in Lung Adenocarcinoma and Its Latent Transcriptional Regulating Mechanism","volume":"89","author":"Yang","year":"2020","journal-title":"Comput. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1053\/j.gastro.2011.01.043","article-title":"Loss of Runx3 Is a Key Event in Inducing Precancerous State of the Stomach","volume":"140","author":"Ito","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"376","DOI":"10.3748\/wjg.v10.i3.376","article-title":"Hemizygous Deletion and Hypermethylation of RUNX3 Gene in Hepatocellular Carcinoma","volume":"10","author":"Xiao","year":"2004","journal-title":"World J. Gastroenterol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1101\/gad.176826.111","article-title":"Pioneer Transcription Factors: Establishing Competence for Gene Expression","volume":"25","author":"Zaret","year":"2011","journal-title":"Genes Dev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4318","DOI":"10.1038\/emboj.2012.275","article-title":"RUNX1 Reshapes the Epigenetic Landscape at the Onset of Haematopoiesis: RUNX1 Shifts Transcription Factor Binding Patterns","volume":"31","author":"Lichtinger","year":"2012","journal-title":"EMBO J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1182\/blood-2008-11-191890","article-title":"Early Chromatin Unfolding by RUNX1: A Molecular Explanation for Differential Requirements during Specification versus Maintenance of the Hematopoietic Gene Expression Program","volume":"114","author":"Hoogenkamp","year":"2009","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7184","DOI":"10.1093\/emboj\/20.24.7184","article-title":"Activation of AML1-Mediated Transcription by MOZ and Inhibition by the MOZ-CBP Fusion Protein","volume":"20","author":"Kitabayashi","year":"2001","journal-title":"EMBO J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6544","DOI":"10.1182\/blood-2010-11-317909","article-title":"The Ability of MLL to Bind RUNX1 and Methylate H3K4 at PU.1 Regulatory Regions Is Impaired by MDS\/AML-Associated RUNX1\/AML1 Mutations","volume":"118","author":"Huang","year":"2011","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"7982","DOI":"10.1128\/MCB.22.22.7982-7992.2002","article-title":"Runx2 (Cbfa1, AML-3) Interacts with Histone Deacetylase 6 and Represses the P21CIP1\/WAF1 Promoter","volume":"22","author":"Westendorf","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5152","DOI":"10.1038\/s41388-020-1351-z","article-title":"Integrative Multi-Omics Analysis of a Colon Cancer Cell Line with Heterogeneous Wnt Activity Revealed RUNX2 as an Epigenetic Regulator of EMT","volume":"39","author":"Yi","year":"2020","journal-title":"Oncogene"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1038\/s41467-019-09810-w","article-title":"RUNX3 Regulates Cell Cycle-Dependent Chromatin Dynamics by Functioning as a Pioneer Factor of the Restriction-Point","volume":"10","author":"Lee","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_73","unstructured":"National Library of Medicine (2023, March 18). RUNX1 RUNX Family Transcription Factor 1 [Homo sapiens (Human)], Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene\/861."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"10431","DOI":"10.1073\/pnas.88.23.10431","article-title":"T(8;21) Breakpoints on Chromosome 21 in Acute Myeloid Leukemia Are Clustered within a Limited Region of a Single Gene, AML1","volume":"88","author":"Miyoshi","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Martinez, M., Hinojosa, M., Trombly, D., Morin, V., Stein, J., Stein, G., Javed, A., and Gutierrez, S.E. (2016). Transcriptional Auto-Regulation of RUNX1 P1 Promoter. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149119"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"188715","DOI":"10.1016\/j.bbcan.2022.188715","article-title":"RUNX1 and Cancer","volume":"1877","author":"Lin","year":"2022","journal-title":"Biochim. Biophys. Acta (BBA) Rev. Cancer"},{"key":"ref_77","unstructured":"(2023, April 03). TIMER2.0. Available online: http:\/\/timer.cistrome.org\/."},{"key":"ref_78","unstructured":"(2023, April 03). GENT2. Available online: http:\/\/gent2.appex.kr\/gent2\/."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nmeth0409-239","article-title":"The UCSC Cancer Genomics Browser","volume":"6","author":"Zhu","year":"2009","journal-title":"Nat. Methods"},{"key":"ref_80","unstructured":"(2023, April 03). UCSC Xena. Available online: http:\/\/xena.ucsc.edu\/welcome-to-ucsc-xena\/."},{"key":"ref_81","first-page":"3633","article-title":"Down-Regulation of RUNX1, RUNX3 and CBFbeta in Hepatocellular Carcinomas in an Early Stage of Hepatocarcinogenesis","volume":"26","author":"Miyagawa","year":"2006","journal-title":"Anticancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s13046-020-01650-7","article-title":"COL4A1 Promotes the Growth and Metastasis of Hepatocellular Carcinoma Cells by Activating FAK-Src Signaling","volume":"39","author":"Wang","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0092-8674(00)00025-8","article-title":"A Role for Hematopoietic Stem Cells in Promoting Angiogenesis","volume":"102","author":"Takakura","year":"2000","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1038\/sj.onc.1208287","article-title":"Runx1 Promotes Angiogenesis by Downregulation of Insulin-like Growth Factor-Binding Protein-3","volume":"24","author":"Iwatsuki","year":"2005","journal-title":"Oncogene"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1158\/0008-5472.CAN-10-0402","article-title":"Repression of Vascular Endothelial Growth Factor Expression by the Runt-Related Transcription Factor 1 in Acute Myeloid Leukemia","volume":"71","author":"Ma","year":"2011","journal-title":"Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Tuo, Z., Zhang, Y., Wang, X., Dai, S., Liu, K., Xia, D., Wang, J., and Bi, L. (2022). RUNX1 Is a Promising Prognostic Biomarker and Related to Immune Infiltrates of Cancer-Associated Fibroblasts in Human Cancers. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-09632-y"},{"key":"ref_87","unstructured":"National Library of Medicine (2023, March 18). RUNX1-IT1 RUNX1 Intronic Transcript 1 [Homo sapiens (Human)], Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene?Db=gene&Cmd=DetailsSearch&Term=80215."},{"key":"ref_88","first-page":"8287","article-title":"LncRNA RUNX1-IT1 Inhibits Proliferation and Promotes Apoptosis of Hepatocellular Carcinoma by Regulating MAPK Pathways","volume":"23","author":"Yan","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41419-020-2274-x","article-title":"LncRNA RUNX1-IT1 Which Is Downregulated by Hypoxia-Driven Histone Deacetylase 3 Represses Proliferation and Cancer Stem-like Properties in Hepatocellular Carcinoma Cells","volume":"11","author":"Sun","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"16573","DOI":"10.18632\/oncotarget.4117","article-title":"Estrogenic Gper Signaling Regulates Mir144 Expression in Cancer Cells and Cancer-Associated Fibroblasts (Cafs)","volume":"6","author":"Vivacqua","year":"2015","journal-title":"Oncotarget"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3325","DOI":"10.3892\/or.2016.5139","article-title":"MicroRNA-455 Regulates Migration and Invasion of Human Hepatocellular Carcinoma by Targeting Runx2","volume":"36","author":"Qin","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Wang, S.-Y., Chen, C.-L., Hu, Y.-C., Chi, Y., Huang, Y.-H., Su, C.-W., Jeng, W.-J., Liang, Y.-J., and Wu, J.-C. (2019). High Expression of MicroRNA-196a Is Associated with Progression of Hepatocellular Carcinoma in Younger Patients. Cancers, 11.","DOI":"10.3390\/cancers11101549"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1002\/cbin.11673","article-title":"Upregulation of OGT by Caveolin-1 Promotes Hepatocellular Carcinoma Cell Migration and Invasion","volume":"45","author":"Wang","year":"2021","journal-title":"Cell Biol. Int."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7366","DOI":"10.1038\/s41598-018-25768-z","article-title":"MiR-23a Transcriptional Activated by Runx2 Increases Metastatic Potential of Mouse Hepatoma Cell via Directly Targeting Mgat3","volume":"8","author":"Huang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e23717","DOI":"10.1002\/jcla.23717","article-title":"LncRNA HAND2-AS1 Overexpression Inhibits Cancer Cell Proliferation in Hepatocellular Carcinoma by Downregulating RUNX2 Expression","volume":"35","author":"Jing","year":"2021","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.1016\/j.cellsig.2014.09.011","article-title":"Tumor Suppressor Long Non-Coding RNA, MT1DP Is Negatively Regulated by YAP and Runx2 to Inhibit FoxA1 in Liver Cancer Cells","volume":"26","author":"Yu","year":"2014","journal-title":"Cell. Signal."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/cas.13901","article-title":"Circ LARP 4 Induces Cellular Senescence through Regulating MiR-761\/RUNX 3\/P53\/P21 Signaling in Hepatocellular Carcinoma","volume":"110","author":"Chen","year":"2019","journal-title":"Cancer Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"61475","DOI":"10.18632\/oncotarget.18424","article-title":"RUNX3 Regulates Hepatocellular Carcinoma Cell Metastasis via Targeting MiR-186\/E-Cadherin\/EMT Pathway","volume":"8","author":"Gou","year":"2017","journal-title":"Oncotarget"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"109168","DOI":"10.1016\/j.intimp.2022.109168","article-title":"TLR2 Agonist Promotes Myeloid-Derived Suppressor Cell Polarization via Runx1 in Hepatocellular Carcinoma","volume":"111","author":"Li","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.devcel.2005.02.013","article-title":"Canonical Wnt\/\u03b2-Catenin Signaling Prevents Osteoblasts from Differentiating into Chondrocytes","volume":"8","author":"Hill","year":"2005","journal-title":"Dev. Cell"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"10549","DOI":"10.1073\/pnas.180309597","article-title":"A RUNX2\/PEBP2 AA\/CBFA1 Mutation Displaying Impaired Transactivation and Smad Interaction in Cleidocranial Dysplasia","volume":"97","author":"Zhang","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.2147\/CMAR.S302173","article-title":"RUNX2 as a Promising Therapeutic Target for Malignant Tumors","volume":"13","author":"Zhao","year":"2021","journal-title":"Cancer Manag. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.3892\/or.2016.5101","article-title":"RUNX2 Promotes Hepatocellular Carcinoma Cell Migration and Invasion by Upregulating MMP9 Expression","volume":"36","author":"Wang","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Cao, Z., Sun, B., Zhao, X., Zhang, Y., Gu, Q., Liang, X., Dong, X., and Zhao, N. (2020). Correction: Cao, Z.; et al. The Expression and Functional Significance of Runx2 in Hepatocellular Carcinoma: Its Role in Vasculogenic Mimicry and Epithelial\u2014Mesenchymal Transition. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms22010077"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e2269","DOI":"10.1038\/cddis.2016.175","article-title":"NUPR1, a New Target in Liver Cancer: Implication in Controlling Cell Growth, Migration, Invasion and Sorafenib Resistance","volume":"7","author":"Emma","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"7277","DOI":"10.1158\/0008-5472.CAN-16-2100","article-title":"CBX4 Suppresses Metastasis via Recruitment of HDAC3 to the Runx2 Promoter in Colorectal Carcinoma","volume":"76","author":"Wang","year":"2016","journal-title":"Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1002\/ijc.27525","article-title":"Runt-Related Transcription Factor 2 in Human Colon Carcinoma: A Potent Prognostic Factor Associated with Estrogen Receptor","volume":"131","author":"Sase","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jcb.10276","article-title":"Runx2, A Multifunctional Transcription Factor in Skeletal Development","volume":"87","author":"Komori","year":"2002","journal-title":"J. Cell. Biochem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"8581","DOI":"10.1128\/MCB.25.19.8581-8591.2005","article-title":"The Runx2 Osteogenic Transcription Factor Regulates Matrix Metalloproteinase 9 in Bone Metastatic Cancer Cells and Controls Cell Invasion","volume":"25","author":"Pratap","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.canlet.2014.03.011","article-title":"RUNX2 Is Overexpressed in Melanoma Cells and Mediates Their Migration and Invasion","volume":"348","author":"Boregowda","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3302","DOI":"10.1158\/0008-5472.CAN-15-0240","article-title":"ITGBL1 Is a Runx2 Transcriptional Target and Promotes Breast Cancer Bone Metastasis by Activating the TGF\u03b2 Signaling Pathway","volume":"75","author":"Li","year":"2015","journal-title":"Cancer Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s12253-015-0018-5","article-title":"Runx2 Expression as a Potential Prognostic Marker in Invasive Ductal Breast Carcinoma","volume":"22","author":"Mostafa","year":"2016","journal-title":"Pathol. Oncol. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/1476-4598-9-258","article-title":"Runx2 Transcriptome of Prostate Cancer Cells: Insights into Invasiveness and Bone Metastasis","volume":"9","author":"Baniwal","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1158\/1535-7163.MCT-13-1060","article-title":"Doxycycline as an Inhibitor of the Epithelial-to-Mesenchymal Transition and Vasculogenic Mimicry in Hepatocellular Carcinoma","volume":"13","author":"Meng","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1002\/hep.23311","article-title":"Expression and Functional Significance of Twist1 in Hepatocellular Carcinoma: Its Role in Vasculogenic Mimicry","volume":"51","author":"Sun","year":"2010","journal-title":"Hepatology"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1093\/glycob\/cwu086","article-title":"Galectin-3 in Angiogenesis and Metastasis","volume":"24","author":"Funasaka","year":"2014","journal-title":"Glycobiology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1161\/ATVBAHA.107.158014","article-title":"VE-Cadherin: The Major Endothelial Adhesion Molecule Controlling Cellular Junctions and Blood Vessel Formation","volume":"28","author":"Vestweber","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"5831","DOI":"10.7150\/jca.45190","article-title":"ZNF521 Which Is Downregulated by MiR-802 Suppresses Malignant Progression of Hepatocellular Carcinoma through Regulating Runx2 Expression","volume":"11","author":"Yang","year":"2020","journal-title":"J. Cancer"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1002\/cbin.10584","article-title":"MicroRNA-455 Suppresses Non-Small Cell Lung Cancer through Targeting ZEB1: The Role of MiRNA-455 in NSCLC","volume":"40","author":"Li","year":"2016","journal-title":"Cell Biol. Int."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1007\/s13277-014-2766-3","article-title":"MicroRNA-455 Inhibits Proliferation and Invasion of Colorectal Cancer by Targeting RAF Proto-Oncogene Serine\/Threonine-Protein Kinase","volume":"36","author":"Chai","year":"2015","journal-title":"Tumor Biol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"D296","DOI":"10.1093\/nar\/gkx1067","article-title":"MiRTarBase Update 2018: A Resource for Experimentally Validated MicroRNA-Target Interactions","volume":"46","author":"Chou","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/nyas.13206","article-title":"Runx2 and MicroRNA Regulation in Bone and Cartilage Diseases: Runx2 and MiRNAs in Bone and Cartilage","volume":"1383","author":"Zhao","year":"2016","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jss.2004.03.028","article-title":"The Role of Osteopontin in Tumor Metastasis","volume":"121","author":"Wai","year":"2004","journal-title":"J. Surg. Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/j.cell.2015.04.048","article-title":"RUNX3 Controls a Metastatic Switch in Pancreatic Ductal Adenocarcinoma","volume":"161","author":"Whittle","year":"2015","journal-title":"Cell"},{"key":"ref_125","first-page":"264","article-title":"UnPAKing RUNX3 Functions\u2013Both Sides of the Coin","volume":"10","author":"Kumar","year":"2017","journal-title":"Small GTPases"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3109\/07357907.2014.1003934","article-title":"RUNX3 Promoter Methylation Is Associated with Hepatocellular Carcinoma Risk: A Meta-Analysis","volume":"33","author":"Zhang","year":"2015","journal-title":"Cancer Investig."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"10333","DOI":"10.1007\/s13277-014-2329-7","article-title":"Clinicopathological Significance of RUNX3 Gene Hypermethylation in Hepatocellular Carcinoma","volume":"35","author":"Yang","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s43042-022-00256-2","article-title":"Relation of the Methylation State of RUNX3 and P16 Gene Promoters with Hepatocellular Carcinoma in Egyptian Patients","volume":"23","author":"Mohamed","year":"2022","journal-title":"Egypt. J. Med. Hum. Genet."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e8279","DOI":"10.1097\/MD.0000000000008279","article-title":"Methylation Analysis of P16, SLIT2, SCARA5, and Runx3 Genes in Hepatocellular Carcinoma","volume":"96","author":"Sun","year":"2017","journal-title":"Medicine"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1080\/09674845.2019.1694123","article-title":"Methylation of Tumour Suppressor Genes RUNX3, RASSF1A and E-Cadherin in HCV-Related Liver Cirrhosis and Hepatocellular Carcinoma","volume":"77","author":"Nour","year":"2020","journal-title":"Br. J. Biomed. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.3892\/or.2015.4515","article-title":"The Emerging Role of RUNX3 in Cancer Metastasis (Review)","volume":"35","author":"Chen","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.yexcr.2009.09.025","article-title":"RUNX3 Directly Interacts with Intracellular Domain of Notch1 and Suppresses Notch Signaling in Hepatocellular Carcinoma Cells","volume":"316","author":"Gao","year":"2010","journal-title":"Exp. Cell Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"6884","DOI":"10.1038\/onc.2017.290","article-title":"Runx3 Plays a Critical Role in Restriction-Point and Defense against Cellular Transformation","volume":"36","author":"Chi","year":"2017","journal-title":"Oncogene"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1002\/jcb.22973","article-title":"Loss of Runt-Related Transcription Factor 3 Causes Development and Progression of Hepatocellular Carcinoma","volume":"112","author":"Shiraha","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1002\/ijc.27575","article-title":"Runt-Related Transcription Factor 3 Reverses Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma","volume":"131","author":"Tanaka","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.3892\/or.2016.4681","article-title":"Loss of Runt-Related Transcription Factor 3 Induces Resistance to 5-Fluorouracil and Cisplatin in Hepatocellular Carcinoma","volume":"35","author":"Kataoka","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.bbrc.2012.07.127","article-title":"Upregulated MiR-130a Increases Drug Resistance by Regulating RUNX3 and Wnt Signaling in Cisplatin-Treated HCC Cell","volume":"425","author":"Xu","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1111\/j.1440-1746.2009.06191.x","article-title":"Hypermethylation Downregulates Runx3 Gene Expression and Its Restoration Suppresses Gastric Epithelial Cell Growth by Inducing P27 and Caspase3 in Human Gastric Cancer","volume":"25","author":"Chen","year":"2010","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"4809","DOI":"10.1158\/0008-5472.CAN-04-3741","article-title":"Loss of RUNX3 Expression Significantly Affects the Clinical Outcome of Gastric Cancer Patients and Its Restoration Causes Drastic Suppression of Tumor Growth and Metastasis","volume":"65","author":"Wei","year":"2005","journal-title":"Cancer Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"8097","DOI":"10.1128\/MCB.25.18.8097-8107.2005","article-title":"RUNX3 Suppresses Gastric Epithelial Cell Growth by Inducing P21WAF1\/Cip1 Expression in Cooperation with Transforming Growth Factor \u03b2-Activated SMAD","volume":"25","author":"Chi","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0959-437X(03)00007-8","article-title":"RUNX Transcription Factors as Key Targets of TGF-\u03b2 Superfamily Signaling","volume":"13","author":"Ito","year":"2003","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"4474","DOI":"10.1128\/MCB.01926-05","article-title":"The RUNX3 Tumor Suppressor Upregulates Bim in Gastric Epithelial Cells Undergoing Transforming Growth Factor\u03b2-Induced Apoptosis","volume":"26","author":"Yano","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"4336","DOI":"10.1038\/sj.onc.1207286","article-title":"Tumor Suppressor Activity of RUNX3","volume":"23","author":"Bae","year":"2004","journal-title":"Oncogene"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"8048","DOI":"10.1073\/pnas.112664499","article-title":"Integration of Runx and Smad Regulatory Signals at Transcriptionally Active Subnuclear Sites","volume":"99","author":"Zaidi","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"70","DOI":"10.4103\/ctm.ctm_22_18","article-title":"Senescence and Cancer","volume":"4","author":"Zeng","year":"2018","journal-title":"Cancer Transl. Med."},{"key":"ref_146","first-page":"188","article-title":"Complex Interplay between the RUNX Transcription Factors and Wnt\/\u03b2-Catenin Pathway in Cancer: A Tango in the Night","volume":"43","author":"Sweeney","year":"2020","journal-title":"Mol. Cells"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1002\/hep.25849","article-title":"Hepatitis C Virus-Induced up-Regulation of MicroRNA-155 Promotes Hepatocarcinogenesis by Activating Wnt Signaling","volume":"56","author":"Zhang","year":"2012","journal-title":"Hepatology"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Giovannini, C., Fornari, F., Piscaglia, F., and Gramantieri, L. (2021). Notch Signaling Regulation in HCC: From Hepatitis Virus to Non-Coding RNAs. Cells, 10.","DOI":"10.3390\/cells10030521"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/S1499-3872(13)60046-6","article-title":"Notchl and Notch4 Are Markers for Poor Prognosis of Hepatocellular Carcinoma","volume":"12","author":"Ahn","year":"2013","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_150","first-page":"523","article-title":"Restored Expression of the Tumor Suppressor Gene RUNX3 Reduces Cancer Stem Cells in Hepatocellular Carcinoma by Suppressing Jagged1-Notch Signaling","volume":"26","author":"Nishina","year":"2011","journal-title":"Oncol. Rep."},{"key":"ref_151","first-page":"770","article-title":"Sorafenib regulates vascular endothelial growth factor by runt-related transcription factor-3 to inhibit angiogenesis in hepatocellular carcinoma","volume":"30","author":"Chai","year":"2022","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1038\/onc.2013.76","article-title":"RUNX3 Inhibits Hypoxia-Inducible Factor-1\u03b1 Protein Stability by Interacting with Prolyl Hydroxylases in Gastric Cancer Cells","volume":"33","author":"Lee","year":"2014","journal-title":"Oncogene"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.jhep.2018.03.019","article-title":"EASL Clinical Practice Guidelines: Management of Hepatocellular Carcinoma","volume":"69","author":"Galle","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nrm3758","article-title":"Molecular Mechanisms of Epithelial\u2013Mesenchymal Transition","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1002\/stem.1183","article-title":"Runx3 Protects Gastric Epithelial Cells Against Epithelial-Mesenchymal Transition-Induced Cellular Plasticity and Tumorigenicity","volume":"30","author":"Voon","year":"2012","journal-title":"Stem Cells"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Loh, C.-Y., Chai, J., Tang, T., Wong, W., Sethi, G., Shanmugam, M., Chong, P., and Looi, C. (2019). The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges. Cells, 8.","DOI":"10.3390\/cells8101118"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"33269","DOI":"10.18632\/oncotarget.5037","article-title":"Targeting of RUNX3 by MiR-130a and MiR-495 Cooperatively Increases Cell Proliferation and Tumor Angiogenesis in Gastric Cancer Cells","volume":"6","author":"Lee","year":"2015","journal-title":"Oncotarget"},{"key":"ref_158","first-page":"2990","article-title":"MicroRNA-130a-3p Promotes the Proliferation and Inhibits the Apoptosis of Cervical Cancer Cells via Negative Regulation of RUNX3","volume":"22","author":"Wang","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.canlet.2020.02.016","article-title":"Synthetic Lethality: A Promising Therapeutic Strategy for Hepatocellular Carcinoma","volume":"476","author":"Tang","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1056\/NEJMoa0708857","article-title":"Sorafenib in Advanced Hepatocellular Carcinoma","volume":"359","author":"Llovet","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/hep.21467","article-title":"Transcriptome Classification of HCC Is Related to Gene Alterations and to New Therapeutic Targets","volume":"45","author":"Boyault","year":"2007","journal-title":"Hepatology"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.jhep.2016.05.035","article-title":"Genetic Profiling of Hepatocellular Carcinoma Using Next-Generation Sequencing","volume":"65","author":"Schulze","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_163","first-page":"436","article-title":"Diverse Modes of Genomic Alteration in Hepatocellular Carcinoma","volume":"15","author":"Jhunjhunwala","year":"2014","journal-title":"Genome Biol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.cell.2017.05.046","article-title":"Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma","volume":"169","author":"Ally","year":"2017","journal-title":"Cell"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"9038","DOI":"10.7150\/thno.63416","article-title":"Mapping the Landscape of Synthetic Lethal Interactions in Liver Cancer","volume":"11","author":"Yang","year":"2021","journal-title":"Theranostics"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1093\/jmcb\/mjy076","article-title":"Functional Relationship between P53 and RUNX Proteins","volume":"11","author":"Bae","year":"2019","journal-title":"J. Mol. Cell Biol."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Krishnan, V. (2023). The RUNX Family of Proteins, DNA Repair, and Cancer. Cells, 12.","DOI":"10.3390\/cells12081106"},{"key":"ref_168","unstructured":"(2023, August 25). Pharos, Available online: https:\/\/pharos.nih.gov\/targets\/RUNX2."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"5182","DOI":"10.4238\/2014.July.7.11","article-title":"Relationship between RUNX3 Methylation and Hepatocellular Carcinoma in Asian Populations: A Systematic Review","volume":"13","author":"Lu","year":"2014","journal-title":"Genet. Mol. Res."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Shahid, I. (2018). Hepatitis C\u2014From Infection to Cure, InTech.","DOI":"10.5772\/intechopen.72268"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/18\/2303\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:53:21Z","timestamp":1760129601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/18\/2303"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,19]]},"references-count":170,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["cells12182303"],"URL":"https:\/\/doi.org\/10.3390\/cells12182303","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,19]]}}}