{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T05:25:19Z","timestamp":1766553919906,"version":"3.48.0"},"reference-count":35,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"crossref","award":["LQ21H200004"],"award-info":[{"award-number":["LQ21H200004"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Objective: This study aims to investigate the functional role of lncRNA STX17-DT, which was previously found to be upregulated in peripheral blood mononuclear cells (PBMCs) of PBC patients, by examining its impact on gene expression and cellular behavior in a human monocyte model. Methods: STX17-DT was overexpressed in THP-1 cells, which was assessed via plasmid transfection. Transcriptomic changes were analyzed by RNA sequencing, followed by comprehensive bioinformatics analyses including differential expression, functional enrichment, transcription factor network, and protein\u2013protein interaction (PPI) analysis. Functional validation was performed using CCK-8 and TUNEL assays to assess proliferation and apoptosis, respectively. Results: Overexpression of STX17-DT led to 1973 differentially expressed genes (DEGs), with 1201 upregulated and 772 downregulated. Key upregulated genes included interferon-stimulated genes (e.g., interferon induced protein 44 like (IFI44L), interferon induced protein 44 (IFI44), guanylate binding protein 1(GBP1)) and chemokines (CCL4, CCL8). Upregulated DEGs were significantly enriched in immune-related pathways such as NF-\u03baB signaling, Toll-like receptor signaling, TNF signaling, and cytokine\u2013cytokine receptor interaction. Downregulated genes were involved in metabolic and signaling pathways such as PI3K\u2013Akt, cAMP, and butanoate metabolism. Transcription factor analysis revealed significant alterations in regulators like Yes1 associated transcriptional regulator(YAP1), nuclear receptor subfamily 4 group A member 1(NR4A1), and MAF bZIP transcription factor B(MAFB). PPI network analysis suggested TNF, TLR4, TLR6, and STAT2 as central hubs. Functionally, STX17-DT overexpression enhanced THP-1 cell proliferation and significantly reduced apoptosis. Conclusions: STX17-DT promoted a pro-inflammatory transcriptomic profile and enhanced monocyte survival in our study, suggesting a potential role in PBC immunopathology. It may represent a potential biomarker and therapeutic target, particularly for patients with advanced disease or suboptimal response to ursodeoxycholic acid. Further studies in primary cells, animal models, and histological samples are warranted to validate its role in PBC pathogenesis.<\/jats:p>","DOI":"10.3390\/genes17010010","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T11:30:18Z","timestamp":1766489418000},"page":"10","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Differentially Expressed Genes and Molecular Pathways Involved in Primary Biliary Cholangitis Using RNA-Seq"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1651-536X","authenticated-orcid":false,"given":"Min","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China"},{"name":"Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou 310016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyun","family":"Shen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endoscopic Technology Research, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haitao","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Laboratory and Blood Transfusion, The 904th Hospital of PLA Joint Logistics Support Force, Wuxi 214007, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China"},{"name":"Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou 310016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1982-273X","authenticated-orcid":false,"given":"Fengying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China"},{"name":"Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou 310016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1111\/hepr.12729","article-title":"Changing nomenclature for PBC from \u201cprimary biliary cirrhosis\u201d to \u201cprimary biliary cholangitis\u201d","volume":"46","author":"Tanaka","year":"2016","journal-title":"Hepatol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3350\/cmh.2020.0028","article-title":"Current understanding of primary biliary cholangitis","volume":"27","author":"Tanaka","year":"2021","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_3","unstructured":"Tan, J.J.-R., Chung, A.H.-L., Loo, J.H., Quek, J.W.E., Sharma, S., Singh, C.L., Yap, R.X.J., Tay, W.X., Smith, M.K., and Lytvyak, E. (Clin. Gastroenterol. Hepatol., 2025). Global Epidemiology of Primary Biliary Cholangitis: An Updated Systematic Review and Meta-analysis, Clin. Gastroenterol. Hepatol., in press."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41395-018-0390-3","article-title":"Diagnosis and Management of Primary Biliary Cholangitis","volume":"114","author":"Younossi","year":"2019","journal-title":"Am. J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s12072-022-10431-7","article-title":"Prediction and evaluation of high-risk patients with primary biliary cholangitis receiving ursodeoxycholic acid therapy: An early criterion","volume":"17","author":"Yang","year":"2023","journal-title":"Hepatol. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/hep.30145","article-title":"Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases","volume":"69","author":"Lindor","year":"2019","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1515\/cclm-2020-0122","article-title":"Evaluation of a novel extended automated particle-based multi-analyte assay for the detection of autoantibodies in the diagnosis of primary biliary cholangitis","volume":"58","author":"Villalta","year":"2020","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1515\/cclm-2017-0249","article-title":"The diagnostic accuracy of biomarkers for diagnosis of primary biliary cholangitis (PBC) in anti-mitochondrial antibody (AMA)-negative PBC patients: A review of literature","volume":"56","author":"Matinato","year":"2017","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41575-019-0226-7","article-title":"Primary biliary cholangitis: Pathogenesis and therapeutic opportunities","volume":"17","author":"Gulamhusein","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"509","DOI":"10.2174\/187152811798104890","article-title":"Modification of chemokine pathways and immune cell infiltration as a novel therapeutic approach in liver inflammation and fibrosis","volume":"10","author":"Zimmermann","year":"2011","journal-title":"Inflamm. Allergy Drug Targets"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Su, X., Jin, W., Liu, L., Zhu, Z., and Li, C. (2023). Regulation of CD47 expression on CD14+ monocytes by interferon-\u03b1 in PBC patients. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1256995"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1002\/hep.21123","article-title":"Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis","volume":"43","author":"Lan","year":"2006","journal-title":"Hepatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/ajg.2009.596","article-title":"PML nuclear body component Sp140 is a novel autoantigen in primary biliary cirrhosis","volume":"105","author":"Granito","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"ref_14","first-page":"374","article-title":"Analysis and functional study on lncRNA expression profile in primary biliary cirrhosis patients","volume":"41","author":"Yang","year":"2018","journal-title":"Chin. J. Lab. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1007\/s10753-022-01713-1","article-title":"Fenofibrate Downregulates NF-\u03baB Signaling to Inhibit Pro-inflammatory Cytokine Secretion in Human THP-1 Macrophages and During Primary Biliary Cholangitis","volume":"45","author":"Gallucci","year":"2022","journal-title":"Inflammation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.atherosclerosis.2011.09.003","article-title":"The use of THP-1 cells as a model for mimicking the function and regulation of monocytes and macrophages in the vasculature","volume":"221","author":"Qin","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nmeth.1938","article-title":"Detecting overlapping protein complexes in protein-protein interaction networks","volume":"9","author":"Nepusz","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1146\/annurev-pathol-020712-164014","article-title":"The immunobiology and pathophysiology of primary biliary cirrhosis","volume":"8","author":"Hirschfield","year":"2013","journal-title":"Annu. Rev. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000337585","article-title":"Reduced hepatic injury in Toll-like receptor 4-deficient mice following D-galactosamine\/lipopolysaccharide-induced fulminant hepatic failure","volume":"29","author":"Avlas","year":"2012","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Jiang, H., Yu, Y., Hu, X., Du, B., Shao, Y., Wang, F., Chen, L., Yan, R., Li, L., and Lv, L. (2024). The fecal microbiota of patients with primary biliary cholangitis (PBC) causes PBC-like liver lesions in mice and exacerbates liver damage in a mouse model of PBC. Gut Microbes, 16.","DOI":"10.1080\/19490976.2024.2383353"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.molmed.2021.12.006","article-title":"Crosstalk between bile acid-activated receptors and microbiome in entero-hepatic inflammation","volume":"28","author":"Thibaut","year":"2022","journal-title":"Trends Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1136\/gutjnl-2021-326500","article-title":"Protective and aggressive bacterial subsets and metabolites modify hepatobiliary inflammation and fibrosis in a murine model of PSC","volume":"72","author":"Awoniyi","year":"2023","journal-title":"Gut"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1053\/j.gastro.2018.02.019","article-title":"Alterations in Intestinal Microbiota Lead to Production of Interleukin 17 by Intrahepatic \u03b3\u03b4 T-Cell Receptor-Positive Cells and Pathogenesis of Cholestatic Liver Disease","volume":"154","author":"Tedesco","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s11274-025-04395-7","article-title":"The gut microbiota-bile acid axis: A crucial regulator of immune function and metabolic health","volume":"41","author":"Tyagi","year":"2025","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_26","first-page":"3951","article-title":"A study of regulatory effects of TLR4 and NF-\u03baB on primary biliary cholangitis","volume":"23","author":"Yu","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1016\/j.dld.2024.05.012","article-title":"ELMO1 regulates macrophage directed migration and attenuates inflammation via NF-\u03baB signaling pathway in primary biliary cholangitis","volume":"56","author":"Ma","year":"2024","journal-title":"Dig. Liver Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13643-024-02460-0","article-title":"Optimal drug regimens for improving ALP biochemical levels in patients with primary biliary cholangitis refractory to UDCA: A systematic review and Bayesian network meta-analysis","volume":"13","author":"Lin","year":"2024","journal-title":"Syst. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Li, X., Liu, R., Wang, Y., Zhu, W., Zhao, D., Wang, X., Yang, H., Gurley, E.C., Chen, W., and Hylemon, P.B. (2020). Cholangiocyte-Derived Exosomal lncRNA H19 Promotes Macrophage Activation and Hepatic Inflammation under Cholestatic Conditions. Cells, 9.","DOI":"10.3390\/cells9010190"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3298","DOI":"10.1016\/j.tjnut.2024.08.012","article-title":"Diet, Microbiome, and Inflammation Predictors of Fecal and Plasma Short-Chain Fatty Acids in Humans","volume":"154","author":"Oliver","year":"2024","journal-title":"J. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Saadh, M.J., Allela, O.Q.B., Ballal, S., Mahdi, M.S., Chahar, M., Verma, R., Al-Hussein, R.K.A., Adil, M., Jawad, M.J., and Al-Nuaimi, A.M.A. (2025). The effects of microbiota-derived short-chain fatty acids on T lymphocytes: From autoimmune diseases to cancer. Semin. Oncol., 52.","DOI":"10.1016\/j.seminoncol.2025.152398"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s11033-025-10714-w","article-title":"Role of the intestinal flora-immunity axis in the pathogenesis of rheumatoid arthritis-mechanisms regulating short-chain fatty acids and Th17\/Treg homeostasis","volume":"52","author":"Lv","year":"2025","journal-title":"Mol. Biol. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Warsop, Z., Anand, N., Al Maliki, H., De Souza, S., Kamyab, A., Al Hadad, A., and Alrubaiy, L. (2024). Up-to-Date Snapshot of Current and Emerging Medical Therapies in Primary Biliary Cholangitis. J. Pers. Med., 14.","DOI":"10.3390\/jpm14121133"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s12016-025-09074-x","article-title":"The Treatment of Primary Biliary Cholangitis: Time for Personalized Medicine","volume":"68","author":"Men","year":"2025","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mitchell, N.E., Chan, S.Y., Diaz, D.J., Ansari, N., Lee, J., and Twohig, P. (2025). Evolving therapeutic landscape of primary biliary cholangitis: A review. World J. Hepatol., 17.","DOI":"10.4254\/wjh.v17.i7.107223"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/1\/10\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T05:20:20Z","timestamp":1766553620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/1\/10"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,22]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["genes17010010"],"URL":"https:\/\/doi.org\/10.3390\/genes17010010","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2025,12,22]]}}}