{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T12:17:30Z","timestamp":1778156250122,"version":"3.51.4"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7252168"],"award-info":[{"award-number":["7252168"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Salivary adenoid cystic carcinoma (SACC) is a malignant salivary gland neoplasm characterized by aggressive local invasion and a marked propensity for metastasis. However, the role of MEOX1 in SACC progression remains poorly defined. In this study, we examined the effects of MEOX1 overexpression on the malignant behavior of SACC cells in vitro and in vivo. Human SACC-83 and SACC-LM cells were transduced with lentiviral vectors encoding MEOX1 or an empty vector control, and cell proliferation, migration, invasion, and cell cycle distribution were assessed using CCK-8, wound healing, Transwell, and flow cytometric assays, respectively. RNA sequencing was performed to characterize transcriptional changes associated with MEOX1 overexpression. In vivo, tumor growth was evaluated in BALB\/c nude mice bearing subcutaneous xenografts, and pulmonary metastatic colonization was assessed using a tail vein injection model. MEOX1 overexpression reduced the proliferation, migration, and invasion of SACC cells in vitro and increased the G2\/M phase fraction. In xenograft models, MEOX1-overexpressing cells formed smaller tumors and showed lower Ki67 staining than control cells. In the experimental lung metastasis model, mice injected with MEOX1-overexpressing cells developed fewer pulmonary metastatic nodules. RNA-seq identified 588 differentially expressed genes associated with MEOX1 overexpression, with enrichment in pathways including cytokine\u2013cytokine receptor interaction, Toll-like receptor signaling, and G protein-coupled receptor signaling. Together, these findings indicate that enforced MEOX1 expression is associated with reduced malignant phenotypes in SACC models and with transcriptomic alterations in pathways related to immune response, G protein-coupled receptor signaling, and DNA damage response.<\/jats:p>","DOI":"10.3390\/cimb48050485","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T10:39:47Z","timestamp":1778150387000},"page":"485","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MEOX1 Inhibits Growth and Metastasis of Salivary Adenoid Cystic Carcinoma"],"prefix":"10.3390","volume":"48","author":[{"given":"Huaxiu","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Disease, National Engineering Research Center of Oral Biomaterials and Digital Medicine Devices, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Disease, National Engineering Research Center of Oral Biomaterials and Digital Medicine Devices, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yajuan","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Disease, National Engineering Research Center of Oral Biomaterials and Digital Medicine Devices, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Disease, National Engineering Research Center of Oral Biomaterials and Digital Medicine Devices, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhanlan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Disease, National Engineering Research Center of Oral Biomaterials and Digital Medicine Devices, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuan-Xiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Disease, National Engineering Research Center of Oral Biomaterials and Digital Medicine Devices, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.ijom.2013.04.006","article-title":"Clinicopathological Study of Distant Metastases of Salivary Adenoid Cystic Carcinoma","volume":"42","author":"Gao","year":"2013","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105764","DOI":"10.1016\/j.oraloncology.2022.105764","article-title":"Baseline Prognostic Factors Affecting Survival in Recurrent and\/or Metastatic Salivary Gland Adenoid Cystic Carcinoma","volume":"126","author":"Lombardi","year":"2022","journal-title":"Oral Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e734","DOI":"10.1002\/mco2.734","article-title":"Adenoid Cystic Carcinoma: Insights from Molecular Characterization and Therapeutic Advances","volume":"5","author":"Jia","year":"2024","journal-title":"MedComm"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1038\/s41416-024-02795-4","article-title":"Systemic Therapy in the Management of Metastatic or Locally Recurrent Adenoid Cystic Carcinoma of the Salivary Glands: A Systematic Review of the Last Decade","volume":"131","author":"Zhou","year":"2024","journal-title":"Br. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12935-024-03230-7","article-title":"EN1 Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma by Regulating the PI3K-AKT Pathway and Epithelial-Mesenchymal Transition","volume":"24","author":"Cui","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1093\/hmg\/3.8.1359","article-title":"Isolation of a Diverged Homeobox Gene, M0X1, from the BRCA1 Region on 17q21 by Solution Hybrid Capture","volume":"3","author":"Futreal","year":"1994","journal-title":"Hum. Mol. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"114068","DOI":"10.1016\/j.biopha.2022.114068","article-title":"The Role of MEOX1 in Non-Neoplastic and Neoplastic Diseases","volume":"158","author":"Zeng","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.diff.2021.05.002","article-title":"Mesenchyme Homeobox 1 Mediated-Promotion of Osteoblastic Differentiation Is Negatively Regulated by Mir-3064-5p","volume":"120","author":"Huang","year":"2021","journal-title":"Differentiation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1186\/s13287-021-02466-8","article-title":"Spatio-Temporal Model of Meox1 Expression Control Involvement of Sca-1-Positive Stem Cells in Neointima Formation through the Synergistic Effect of Rho\/CDC42 and SDF-1\u03b1\/CXCR4","volume":"12","author":"Wu","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/s41586-021-03674-1","article-title":"A Transcriptional Switch Governs Fibroblast Activation in Heart Disease","volume":"595","author":"Alexanian","year":"2021","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e31442","DOI":"10.1002\/jcp.31442","article-title":"MEOX1 Triggers Myofibroblast Apoptosis Resistance, Contributing to Pulmonary Fibrosis in Mice","volume":"239","author":"Jin","year":"2024","journal-title":"J. Cell. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12188","DOI":"10.1074\/jbc.RA119.010710","article-title":"Combined P53- and PTEN-Deficiency Activates Expression of Mesenchyme Homeobox 1 (MEOX1) Required for Growth of Triple-Negative Breast Cancer","volume":"295","author":"Gasparyan","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13048-024-01384-6","article-title":"Unraveling the Molecular Mechanisms of Lymph Node Metastasis in Ovarian Cancer: Focus on MEOX1","volume":"17","author":"Li","year":"2024","journal-title":"J. Ovarian Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Thiaville, M.M., Stoeck, A., Chen, L., Wu, R.-C., Magnani, L., Oidtman, J., Shih, I.-M., Lupien, M., and Wang, T.-L. (2012). Identification of PBX1 Target Genes in Cancer Cells by Global Mapping of PBX1 Binding Sites. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036054"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1002\/hed.28132","article-title":"Survival Outcomes in Adenoid Cystic Carcinoma of the Head and Neck: A Systematic Review of 17 497 Cases and Meta-analysis","volume":"47","author":"Lavareze","year":"2025","journal-title":"Head Neck"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/s41392-021-00842-7","article-title":"MEOX1: A Novel Druggable Target That Orchestrates the Activation of Fibroblasts in Cardiac Fibrosis","volume":"6","author":"Schumacher","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3543","DOI":"10.1016\/j.apsb.2024.04.013","article-title":"Ailanthone Ameliorates Pulmonary Fibrosis by Suppressing JUN-Dependent MEOX1 Activation","volume":"14","author":"Zhao","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1002\/tox.23416","article-title":"MEOX1 Suppresses the Progression of Lung Cancer Cells by Inhibiting the Cell-Cycle Checkpoint Gene CCNB1","volume":"37","author":"Xiao","year":"2022","journal-title":"Environ. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41571-021-00565-2","article-title":"Treatment Landscape of Triple-Negative Breast Cancer\u2014Expanded Options, Evolving Needs","volume":"19","author":"Bianchini","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/j.jhep.2022.05.043","article-title":"Multimodal Single-Cell Profiling of Intrahepatic Cholangiocarcinoma Defines Hyperactivated Tregs as a Potential Therapeutic Target","volume":"77","author":"Alvisi","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/nature10933","article-title":"The Clonal and Mutational Evolution Spectrum of Primary Triple-Negative Breast Cancers","volume":"486","author":"Shah","year":"2012","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1158\/2159-8290.CD-13-0136","article-title":"Contribution of P53 to Metastasis","volume":"4","author":"Powell","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.15252\/emmm.201404402","article-title":"Combined Deletion of PTen and P53 in Mammary Epithelium Accelerates Triple-negative Breast Cancer with Dependency on e EF2K","volume":"6","author":"Liu","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"51408","DOI":"10.18632\/oncotarget.9839","article-title":"Novel Cancer Stem Cell Targets during Epithelial to Mesenchymal Transition in PTEN-Deficient Trastuzumab-Resistant Breast Cancer","volume":"7","author":"Sun","year":"2016","journal-title":"Oncotarget"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"143","DOI":"10.21037\/atm-21-6748","article-title":"A Novel 12-Gene Prognostic Signature in Breast Cancer Based on the Tumor Microenvironment","volume":"10","author":"Zhu","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.stem.2017.06.003","article-title":"Muscle Stem Cells Undergo Extensive Clonal Drift during Tissue Growth via Meox1-Mediated Induction of G2 Cell-Cycle Arrest","volume":"21","author":"Nguyen","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.canlet.2005.05.049","article-title":"Chromosome 6 Deletion and Candidate Tumor Suppressor Genes in Adenoid Cystic Carcinoma","volume":"236","author":"Rutherford","year":"2006","journal-title":"Cancer Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.2147\/OTT.S98534","article-title":"miR-98 Functions as a Tumor Suppressor in Salivary Adenoid Cystic Carcinomas","volume":"2016","author":"Liu","year":"2016","journal-title":"OncoTargets Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s10529-015-2007-x","article-title":"MicroRNA-144-3p Inhibits Proliferation and Induces Apoptosis of Human Salivary Adenoid Carcinoma Cells via Targeting of mTOR","volume":"38","author":"Huo","year":"2016","journal-title":"Biotechnol. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1111\/odi.13841","article-title":"miR-5191 Acts as a Tumor Suppressor in Salivary Adenoid Cystic Carcinoma by Targeting Notch-2","volume":"28","author":"Li","year":"2022","journal-title":"Oral Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1007\/s10735-025-10504-5","article-title":"miR-429 Suppresses Progression and Metastasis of Salivary Adenoid Cystic Carcinoma by Targeting ZEB1","volume":"56","author":"Li","year":"2025","journal-title":"J. Mol. Histol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/gcc.22312","article-title":"Potential Role for Inhibition of Protein Phosphatase 2A Tumor Suppressor in Salivary Gland Malignancies","volume":"55","author":"Routila","year":"2016","journal-title":"Genes Chromosomes Cancer"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/5\/485\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:57:00Z","timestamp":1778155020000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/5\/485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,6]]},"references-count":32,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["cimb48050485"],"URL":"https:\/\/doi.org\/10.3390\/cimb48050485","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,6]]}}}