{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:16:26Z","timestamp":1791317786375,"version":"4.3.1"},"reference-count":59,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Atrium Health Research Fund: Internal funding"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sj\u00f6gren\u2019s disease (SjD) is an autoimmune disease of exocrine tissues. Prior research has shown that ETS proto-oncogene 1 (ETS1), STAT1, and IL33 may contribute to the disease\u2019s pathology. However, the regulatory mechanisms of these genes remain poorly characterized. Our objective was to explore the mechanisms of SjD pathology and to identify dysfunctional regulators of these genes by immunostimulation of SjD and sicca relevant cell lines. We used immortalized salivary gland epithelial cell lines (iSGECs) from Sj\u00f6gren\u2019s disease (pSS1) and sicca (nSS2) patients, previously developed in our lab, and control cell line A253 to dose with immunostimulants IFN-\u03b3 or poly(I:C) (0 to 1000 ng\/mL and 0 to 1000 \u00b5g\/mL, respectively) over a 72 h time course. Gene expression was determined using qRT-PCR delta-delta-CT method based on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for mRNA and U6 small nuclear RNA 1 (U6) for miRNA, using normalized relative fold changes 48 h post-immunostimulation. Protein expression was quantified 72 h post-stimulation by Western blotting. Reference-based RNA-seq of immunostimulated pSS1 and nSS2 cells was performed to characterize the reactome of genes conserved across all used doses. The expression of ETS1 and STAT1 protein was upregulated (p &lt; 0.05) in IFN-\u03b3-treated pSS1 and nSS2, as compared to A253 cells. IFN-\u03b3-treated nSS2 cell showed significant IL33 upregulation. Also, IL33 had a correlated (p &lt; 0.01) U-shaped response for low-mid-range doses for IFN-\u03b3- and poly(I:C)-treated pSS1 cells. RNA-seq showed 175 conserved differentially expressed (DE) genes between nSS2 and pSS1 immunostimulated cells. Of these, 44 were shown to interact and 39 were more abundant (p &lt; 0.05) in pSS1 cells. Western blotting demonstrated nSS2 cells expressing ETS1 uniformly across treatments compared to pSS1 cells, despite similar mRNA abundance. miR-145b and miR-193b were significantly under-expressed in IFN-\u03b3-treated nSS2 cells compared to pSS1 cells (p &lt; 0.01). ETS1 and IL33 showed disproportionate mRNA and protein abundances between immunostimulated Sj\u00f6gren\u2019s disease-derived (pSS1), and sicca-derived (nSS2) cell lines. Such differences could be explained by higher levels of miR-145b and miR-193b present in pSS1 cells. Also, RNA-seq results suggested an increased sensitivity of pSS1 cells to immunostimulation. These results reflect current pathobiology aspects, confirming the relevance of immortalized salivary gland epithelial cell lines.<\/jats:p>","DOI":"10.3390\/ijms26125881","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T08:43:58Z","timestamp":1750322638000},"page":"5881","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Elucidating Regulatory Mechanisms of Genes Involved in Pathobiology of Sj\u00f6gren\u2019s Disease: Immunostimulation Using a Cell Culture Model"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0566-3623","authenticated-orcid":false,"given":"Daniel D.","family":"Kepple","sequence":"first","affiliation":[{"name":"Translational Research Laboratories, Department of Oral Medicine\/Oral & Maxillofacial Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Thornburg","sequence":"additional","affiliation":[{"name":"Translational Research Laboratories, Department of Oral Medicine\/Oral & Maxillofacial Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micaela F.","family":"Beckman","sequence":"additional","affiliation":[{"name":"Translational Research Laboratories, Department of Oral Medicine\/Oral & Maxillofacial Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8903-333X","authenticated-orcid":false,"given":"Farah","family":"Bahrani Mougeot","sequence":"additional","affiliation":[{"name":"Translational Research Laboratories, Department of Oral Medicine\/Oral & Maxillofacial Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA"},{"name":"Department of Otolaryngology\/Head & Neck Surgery, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8953-1769","authenticated-orcid":false,"given":"Jean-Luc C.","family":"Mougeot","sequence":"additional","affiliation":[{"name":"Translational Research Laboratories, Department of Oral Medicine\/Oral & Maxillofacial Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA"},{"name":"Department of Otolaryngology\/Head & Neck Surgery, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"ref_1","unstructured":"Carsons, S.E., and Patel, B.C. (2022, August 01). Sjogren Syndrome, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK431049\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1111\/joim.13451","article-title":"Primary Sj\u00f6gren\u2019s syndrome: Longitudinal real-world, observational data on health-related quality of life","volume":"291","author":"Tarn","year":"2022","journal-title":"J. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.7150\/ijms.17718","article-title":"Reviewing primary Sj\u00f6gren\u2019s syndrome: Beyond the dryness\u2014From pathophysiology to diagnosis and treatment","volume":"14","author":"Both","year":"2017","journal-title":"Int. J. Med. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1002\/acr.24014","article-title":"Association of Sj\u00f6gren\u2019s Syndrome With Reduced Lifetime Sex Hormone Exposure: A Case-Control Study","volume":"72","author":"McCoy","year":"2020","journal-title":"Arthritis Care Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Parisis, D., Chivasso, C., Perret, J., Soyfoo, M.S., and Delporte, C. (2020). Current State of Knowledge on Primary Sj\u00f6gren\u2019s Syndrome, an Autoimmune Exocrinopathy. J. Clin. Med., 9.","DOI":"10.3390\/jcm9072299"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e13528","DOI":"10.1097\/MD.0000000000013528","article-title":"Association between Helicobacter pylori infection and Sj\u00f6gren syndrome: A meta-analysis","volume":"97","author":"Chen","year":"2018","journal-title":"Medicine"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sanosyan, A., Daien, C., Nutz, A., Bollore, K., Bedin, A.-S., Morel, J., Zimmermann, V., Nocturne, G., Peries, M., and Guigue, N. (2019). Discrepancy of Serological and Molecular Patterns of Circulating Epstein-Barr Virus Reactivation in Primary Sj\u00f6gren\u2019s Syndrome. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01153"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Maslinska, M., and Kostyra-Grabczak, K. (2022). The role of virus infections in Sj\u00f6gren\u2019s syndrome. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.823659"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1002\/1529-0131(200012)43:12<2807::AID-ANR22>3.0.CO;2-M","article-title":"Differential expression of matrix metalloproteinases in labial salivary glands of patients with primary Sj\u00f6gren\u2019s syndrome","volume":"43","author":"Goicovich","year":"2000","journal-title":"Arthritis Rheum."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1093\/rheumatology\/kez142","article-title":"Treatment of Sj\u00f6gren\u2019s syndrome: Current therapy and future directions","volume":"60","author":"Fox","year":"2021","journal-title":"Rheumatology"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Srivastava, A., and Makarenkova, H.P. (2020). Innate Immunity and Biological Therapies for the Treatment of Sj\u00f6gren\u2019s Syndrome. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239172"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1111\/j.1600-0714.2011.01042.x","article-title":"Cell apoptosis and proliferation in salivary glands of Sj\u00f6gren\u2019s syndrome","volume":"40","author":"Busamia","year":"2011","journal-title":"J. Oral. Pathol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kaneko, N., Chen, H., Perugino, C.A., Maehara, T., Munemura, R., Yokomizo, S., Sameshima, J., Diefenbach, T.J., Premo, K.R., and Chinju, A. (2022). Cytotoxic CD8+ T cells may be drivers of tissue destruction in Sj\u00f6gren\u2019s syndrome. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-19397-w"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhou, J., Zhang, X., and Yu, Q. (2022). Plasmacytoid dendritic cells promote the pathogenesis of Sj\u00f6gren\u2019s syndrome. Biochim. Et. Biophys. Acta (BBA)\u2014Mol. Basis Disease., 1868.","DOI":"10.1016\/j.bbadis.2021.166302"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41584-021-00605-2","article-title":"Epithelial-immune cell interplay in primary Sj\u00f6gren syndrome salivary gland pathogenesis","volume":"17","author":"Verstappen","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1080\/15027732.1986.12461378","article-title":"Focus score in the diagnosis of Sj\u00f6gren\u2019s syndrome","volume":"61","author":"Konttinen","year":"1986","journal-title":"Scand. J. Rheumatol. Suppl."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.autrev.2015.07.002","article-title":"Anti-SSA\/SSB-negative Sj\u00f6gren\u2019s syndrome shows a lower prevalence of lymphoproliferative manifestations, and a lower risk of lymphoma evolution","volume":"14","author":"Quartuccio","year":"2015","journal-title":"Autoimmun Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/acr.23264","article-title":"Natural History and Predictors of Progression to Sj\u00f6gren\u2019s Syndrome Among Participants of the Sj\u00f6gren\u2019s International Collaborative Clinical Alliance Registry","volume":"70","author":"Shiboski","year":"2018","journal-title":"Arthritis Care Res."},{"key":"ref_19","first-page":"e12996","article-title":"Not all Sicca is Sj\u00f6gren\u2019s and not all Sj\u00f6gren\u2019s is Sicca","volume":"13","author":"Neumann","year":"2021","journal-title":"Cureus"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"701581","DOI":"10.3389\/fimmu.2021.701581","article-title":"Inflammatory Stratification in Primary Sj\u00f6gren\u2019s Syndrome Reveals Novel Immune Cell Alterations in Patients\u2019 Minor Salivary Glands","volume":"12","author":"Bharaj","year":"2021","journal-title":"Front Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.cccn.2004.03.006","article-title":"Increase in the ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 in saliva from patients with primary Sj\u00f6gren\u2019s syndrome","volume":"345","author":"Asatsuma","year":"2004","journal-title":"Clin. Chim. Acta."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102756","DOI":"10.1016\/j.autrev.2021.102756","article-title":"Pathophysiologic role of Interleukin-33\/ST2 in Sj\u00f6gren\u2019s syndrome","volume":"20","author":"Soyfoo","year":"2021","journal-title":"Autoimmun Rev."},{"key":"ref_23","first-page":"13","article-title":"Genome-wide association study identifies Sj\u00f6gren\u2019s risk loci with functional implications in immune and glandular cells","volume":"27","author":"Khatri","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nri.2016.95","article-title":"Interleukin-33 in health and disease","volume":"16","author":"Liew","year":"2016","journal-title":"Nat. Rev. Immunology."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Noll, B., Mougeot, F.B., Brennan, M.T., and Mougeot, J.C. (2022). Regulation of MMP9 transcription by ETS1 in immortalized salivary gland epithelial cells of patients with salivary hypofunction and primary Sj\u00f6gren\u2019s syndrome. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-18576-z"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5487","DOI":"10.1016\/j.febslet.2005.09.012","article-title":"Inhibition of matrix metalloproteinase-9 by interferons and TGF-beta1 through distinct signalings accounts for reduced monocyte invasiveness","volume":"579","author":"Nguyen","year":"2005","journal-title":"FEBS Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1186\/s13075-017-1400-3","article-title":"Biosemantics guided gene expression profiling of Sj\u00f6gren\u2019s syndrome: A comparative analysis with systemic lupus erythematosus and rheumatoid arthritis","volume":"19","author":"Shah","year":"2017","journal-title":"Arthritis Res Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/odi.12985","article-title":"Expression of ETS1 and LEF1 in salivary glands of Sj\u00f6gren syndrome patients","volume":"25","author":"Shah","year":"2019","journal-title":"Oral Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-407190-2.00001-0","article-title":"Understanding the role of ETS-mediated gene regulation in complex biological processes","volume":"119","author":"Findlay","year":"2013","journal-title":"Adv. Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1158\/0008-5472.CAN-10-2435","article-title":"Mir-125B is methylated and functions as a tumor suppressor by regulating the ETS1 proto-oncogene in human invasive breast cancer","volume":"71","author":"Zhang","year":"2011","journal-title":"Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.1016\/j.ejca.2010.06.127","article-title":"MicroRNA-193B regulates proliferation, migration and invasion in human hepatocellular carcinoma cells","volume":"46","author":"Xu","year":"2010","journal-title":"Eur. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/gm108","article-title":"Discovery of microvascular mirnas using public gene expression data: Mir-145 is expressed in pericytes and is a regulator of FLI1","volume":"1","author":"Larsson","year":"2009","journal-title":"Genome Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1038\/jid.2012.185","article-title":"Regulation of IL-33 expression by IFN-\u03b3 and tumor necrosis factor-\u03b1 in normal human epidermal keratinocytes","volume":"132","author":"Meephansan","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6774","DOI":"10.1038\/ncomms7774","article-title":"Microrna29a regulates il-33-mediated tissue remodelling in tendon disease","volume":"6","author":"Millar","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1111\/jop.13099","article-title":"Distinct microRNA expression profiles in saliva and salivary gland tissue differentiate patients with primary Sj\u00f6gren\u2019s syndrome from non-Sj\u00f6gren\u2019s sicca patients","volume":"49","author":"Locht","year":"2020","journal-title":"J. Oral Pathol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1002\/art.39214","article-title":"Prediction of Sj\u00f6gren\u2019s Syndrome Years Before Diagnosis and Identification of Patients With Early Onset and Severe Disease Course by Autoantibody Profiling","volume":"67","author":"Theander","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.molcel.2012.08.032","article-title":"Stress-induced alternative splicing provides a mechanism for the regulation of MicroRNA processing in Arabidopsis thaliana","volume":"48","author":"Yan","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1007\/s00018-012-1243-7","article-title":"Review of Ets1 structure, function, and roles in immunity","volume":"70","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1098\/rstb.2001.1029","article-title":"Fibrillin: From Microfibril Assembly to biomechanical function","volume":"357","author":"Kielty","year":"2002","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0024-3205(96)00135-X","article-title":"Interleukin-1 signal transduction","volume":"59","author":"Kalli","year":"1996","journal-title":"Life Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Luo, H., and Zhou, X. (2022). Bioinformatics analysis of potential common pathogenic mechanisms for COVID-19 infection and primary Sjogren\u2019s syndrome. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.938837"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Hynne, H., Aqrawi, L.A., Jensen, J.L., Thiede, B., Palm, \u00d8., Amdal, C.D., Westgaard, K.L., Herlofson, B.B., Utheim, T.P., and Galtung, H.K. (2022). Proteomic Profiling of Saliva and Tears in Radiated Head and Neck Cancer Patients as Compared to Primary Sj\u00f6gren\u2019s Syndrome Patients. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073714"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/1742-4690-8-95","article-title":"Human HERC5 restricts an early stage of HIV-1 assembly by a mechanism correlating with the ISGylation of Gag","volume":"8","author":"Woods","year":"2011","journal-title":"Retrovirology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.1399-0004.1987.tb03316.x","article-title":"Carrier detection of haemophilia A using DNA markers in families with an isolated affected male","volume":"32","author":"Grover","year":"1987","journal-title":"Clin. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Chen, H.-H., Ma, K.S.-K., Dong, C., Chang, W.-J., Gao, K.-R., Perng, W.-T., Huang, J.-Y., and Wei, J.C.-C. (2022). Risk of primary Sjogren\u2019s Syndrome following human papillomavirus infections: A nationwide population-based cohort study. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.967040"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"eabf9564","DOI":"10.1126\/sciimmunol.abf9564","article-title":"Heterozygous OAS1 gain-of-function variants cause an autoinflammatory immunodeficiency","volume":"6","author":"Magg","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Noll, B.D., Grdzelishvili, A., Brennan, M.T., Mougeot, F.B., and Mougeot, J.C. (2020). Immortalization of Salivary Gland Epithelial Cells of Xerostomic Patients: Establishment and Characterization of Novel Cell Lines. J. Clin. Med., 9.","DOI":"10.3390\/jcm9123820"},{"key":"ref_48","unstructured":"Rasband, W.S. (2024, September 09). ImageJ, Available online: https:\/\/imagej.net\/ij\/."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12760","DOI":"10.1128\/JVI.01881-12","article-title":"Double-stranded RNA induces biphasic STAT1 phosphorylation by both type I interferon (IFN)-dependent and type I IFN-independent pathways","volume":"86","author":"Dempoya","year":"2012","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Workman, M.J., Troisi, E., Targan, S.R., Svendsen, C.N., and Barrett, R.J. (2020). Modeling Intestinal Epithelial Response to Interferon-\u03b3 in Induced Pluripotent Stem Cell-Derived Human Intestinal Organoids. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010288"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1038\/sj.jid.5700294","article-title":"SOCS1-negative feedback of STAT1 activation is a key pathway in the dsRNA-induced innate immune response of human keratinocytes","volume":"126","author":"Dai","year":"2006","journal-title":"J. Investig. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.3892\/mmr.2014.2507","article-title":"Toll-like receptor (TLR) expression and TLR-mediated interleukin-8 production by human submandibular gland epithelial cells","volume":"10","author":"Ohta","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_53","first-page":"e140","article-title":"Data quality aware analysis of differential expression in RNA-seq with NOISeq R\/Bioc package","volume":"43","author":"Tarazona","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Starr, A., Nickoloff-Bybel, E., Abedalthaqafi, R., Albloushi, N., and Jordan-Sciutto, K.L. (2023). Human iPSC-derived neurons reveal NMDAR-independent dysfunction following HIV-associated insults. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1353562"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s00425-024-04347-9","article-title":"Transcriptome analysis in Aegilops tauschii unravels further insights into genetic control of stripe rust resistance","volume":"259","author":"Davoudnia","year":"2024","journal-title":"Planta"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13046-023-02936-2","article-title":"DCAF13 inhibits the p53 signaling pathway by promoting p53 ubiquitination modification in lung adenocarcinoma","volume":"43","author":"Wei","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Garcia-Moreno, A., L\u00f3pez-Dom\u00ednguez, R., Villatoro-Garc\u00eda, J.A., Ramirez-Mena, A., Aparicio-Puerta, E., Hackenberg, M., Pascual-Montano, A., and Carmona-Saez, P. (2022). Functional Enrichment Analysis of regulatory elements. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030590"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","article-title":"Functional mapping and annotation of genetic associations with FUMA","volume":"8","author":"Watanabe","year":"2017","journal-title":"Nat. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5881\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:54:57Z","timestamp":1760032497000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5881"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,19]]},"references-count":59,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125881"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125881","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,19]]}}}