{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T08:02:14Z","timestamp":1772611334651,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education and Science of Russia","award":["075-15-2021-1356"],"award-info":[{"award-number":["075-15-2021-1356"]}]},{"name":"Ministry of Education and Science of Russia","award":["24-45-00031"],"award-info":[{"award-number":["24-45-00031"]}]},{"name":"Russian Science Foundation","award":["075-15-2021-1356"],"award-info":[{"award-number":["075-15-2021-1356"]}]},{"name":"Russian Science Foundation","award":["24-45-00031"],"award-info":[{"award-number":["24-45-00031"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>There is still much to learn about the epigenetic mechanisms controlling gene expression during carcinogenesis. When researching aberrant DNA methylation, active proliferative tumor cells from head and neck squamous cell cancer (HNSCC) can be used as a model. The aim of the study was to investigate the methylation status of CDKN1, CDKN2A, MYC, Smad3, SP1, and UBC genes in tumor tissue (control-normal tissue) in 50 patients (37 men and 13 women) with HPV-negative HNSCC. Methods: Bisulfite conversion methods and methyl-sensitive analysis of high-resolution melting curves were used to quantify the methylation of genes. In all patients and across various subgroups (tongue carcinoma, laryngeal and other types of carcinomas T2, T3, T4 status; age before and after 50 years; smoking and non-smoking), there are consistent differences in the methylation levels in the SP1 gene in tumor DNA compared to normal. Results: The methylation of the SP1 gene in tumor DNA suppresses its expression, hinders HNSCC cell proliferation regulation, and could be a molecular indicator of malignant cell growth. The study of DNA methylation of various genes involved in carcinogenesis is promising because hypermethylated promoters can serve as potential biomarkers of disease.<\/jats:p>","DOI":"10.3390\/genes15030281","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T10:47:30Z","timestamp":1708685250000},"page":"281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["SP1 Gene Methylation in Head and Neck Squamous Cell Cancer in HPV-Negative Patients"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8226-0433","authenticated-orcid":false,"given":"Enar","family":"Jumaniyazova","sequence":"first","affiliation":[{"name":"Institute of Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, 117198 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Aghajanyan","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, 117198 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Kurevlev","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, 117198 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leyla","family":"Tskhovrebova","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, 117198 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey","family":"Makarov","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, 117198 Moscow, Russia"},{"name":"Histology Department, Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian Federation, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3146-5615","authenticated-orcid":false,"given":"Konstantin","family":"Gordon","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, 117198 Moscow, Russia"},{"name":"A. Tsyb Medical Radiological Research Center, Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation (A. Tsyb MRRC), 4, Korolev Street, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasiya","family":"Lokhonina","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, 117198 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timur","family":"Fatkhudinov","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, 117198 Moscow, Russia"},{"name":"Avtsyn Research Institute of Human Morphology of Petrovsky National Research Centre of Surgery, 3 Tsyurupy Street, 117418 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Barsouk, A., Aluru, J.S., Rawla, P., Saginala, K., and Barsouk, A. (2023). Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. Med. Sci., 11.","DOI":"10.3390\/medsci11020042"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"915","DOI":"10.21037\/atm-20-6264","article-title":"Molecular landscape of head and neck cancer and implications for therapy","volume":"9","author":"Farah","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6758","DOI":"10.1158\/1078-0432.CCR-09-0784","article-title":"Human papillomavirus in head and neck cancer: Its role in pathogenesis and clinical implications","volume":"15","author":"Chung","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Burkitt, K. (2023). Role of DNA Methylation Profiles as Potential Biomarkers and Novel Therapeutic Targets in Head and Neck Cancer. Cancers, 15.","DOI":"10.3390\/cancers15194685"},{"key":"ref_5","first-page":"7536","article-title":"Comprehensive genomic characterization of head and neck squamous cell carcinomas","volume":"517","author":"Lawrence","year":"2015","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/978-3-319-43624-1_7","article-title":"The role of DNA methylation in cancer","volume":"945","author":"Lakshminarasimhan","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Locke, W.J., Guanzon, D., Ma, C., Liew, Y.J., Duesing, K.R., Fung, K.Y.C., and Ross, J.P. (2019). DNA Methylation Cancer Biomarkers: Translation to the Clinic. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.01150"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nrg3230","article-title":"Functions of DNA methylation: Islands, start sites, gene bodies and beyond","volume":"13","author":"Jones","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Camuzi, D., de Almeida Sim\u00e3o, T., Dias, F., Pinto, L.F.R., and Soares-Lima, S.C. (2021). Head and neck cancers are not alike when tarred with the same brush: An epigenetic perspective from the cancerization field to prognosis. Cancers, 13.","DOI":"10.3390\/cancers13225630"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Liouta, G., Adamaki, M., Tsintarakis, A., Zoumpourlis, P., Liouta, A., Agelaki, S., and Zoumpourlis, V. (2023). DNA Methylation as a Diagnostic, Prognostic, and Predictive Biomarker in Head and Neck Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032996"},{"key":"ref_11","first-page":"v","article-title":"Epigenetic alterations in oncogenesis preface","volume":"754","author":"Karpf","year":"2013","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.4161\/epi.29785","article-title":"Promoter hypermethylation using 24-gene array in early head and neck cancer: Better outcome in oral than in oropharyngeal cancer","volume":"9","author":"Noorlag","year":"2014","journal-title":"Epigenetics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0092-8674(83)90210-6","article-title":"The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter","volume":"35","author":"Dynan","year":"1983","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/jcp.1111","article-title":"Sp1 and Kr\u00fcppel-like factor family of transcription factors in cell growth regulation and cancer","volume":"188","author":"Black","year":"2001","journal-title":"J. Cell. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1242\/dev.106054","article-title":"A crucial role for the ubiquitously expressed transcription factor Sp1 at early stages of hematopoietic specification","volume":"141","author":"Gilmour","year":"2014","journal-title":"Development"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/febs.13148","article-title":"Sp1 and the \u2018hallmarks of cancer\u2019","volume":"282","author":"Beishline","year":"2015","journal-title":"FEBS J."},{"key":"ref_17","first-page":"ZC09","article-title":"Promoter hypermethylation profile of tumour suppressor genes in oral leukoplakia and oral squamous cell carcinoma","volume":"8","author":"Asokan","year":"2014","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1158\/1055-9965.EPI-07-2791","article-title":"Sp1, a new biomarker that identifies a subset of aggressive pancreatic ductal adenocarcinoma","volume":"17","author":"Jiang","year":"2008","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1002\/ijc.26049","article-title":"Sp1 is upregulated in human glioma, promotes MMP-2-mediated cell invasion and predicts poor clinical outcome","volume":"130","author":"Guan","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_20","first-page":"6371","article-title":"Transcription Factor Sp1 Expression Is a Significant Predictor of Survival in Human Gastric Cancer","volume":"9","author":"Wang","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_21","first-page":"9","article-title":"Expression and prognostic value of transcriptional factor sp1 in breast cancer","volume":"26","author":"Wang","year":"2007","journal-title":"Ai Zheng"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"101417","DOI":"10.1016\/j.mcp.2019.06.007","article-title":"Sp1 promotes cell migration and invasion in oral squamous cell carcinoma by upregulating Annexin A2 transcription","volume":"46","author":"Liu","year":"2019","journal-title":"Mol. Cell. Probes"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.oraloncology.2014.07.010","article-title":"MiR-29b suppresses proliferation, migration, and invasion of tongue squamous cell carcinoma through PTEN-AKT signaling pathway by targeting Sp1","volume":"50","author":"Jia","year":"2014","journal-title":"Oral Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.3892\/ijo.2015.2972","article-title":"Downregulation of Sp1 is involved in \u03b2-lapachone-induced cell cycle arrest and apoptosis in oral squamous cell carcinoma","volume":"46","author":"Jeon","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1111\/cpr.12287","article-title":"MicroRNA-137 suppresses tongue squamous carcinoma cell proliferation, migration and invasion","volume":"49","author":"Sun","year":"2016","journal-title":"Cell Prolif."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrc.2018.11","article-title":"The molecular landscape of head and neck cancer","volume":"18","author":"Leemans","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1001\/archoto.2008.540","article-title":"Genomewide gene expression profiles of HPV-positive and HPV-negative oropharyngeal cancer potential implications for treatment choices","volume":"135","author":"Lohavanichbutr","year":"2009","journal-title":"Arch. Otolaryngol.-Head Neck Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/gm453","article-title":"Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors","volume":"5","author":"Lechner","year":"2013","journal-title":"Genome Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1634\/theoncologist.10-3-176","article-title":"FDA Drug Approval Summary: Azacitidine (5-azacytidine, VidazaTM) for Injectable Suspension","volume":"10","author":"Kaminskas","year":"2005","journal-title":"Oncologist"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1146\/annurev-med-111314-035900","article-title":"Epigenetic therapeutics: A new weapon in the war against cancer","volume":"67","author":"Ahuja","year":"2016","journal-title":"Annu. Rev. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13148-019-0663-8","article-title":"Identification of a novel quinoline-based DNA demethylating compound highly potent in cancer cells","volume":"11","author":"Zwergel","year":"2019","journal-title":"Clin. Epigenetics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/s41419-020-02934-8","article-title":"Combined inhibition of JAK1\/2 and DNMT1 by newly identified small-molecule compounds synergistically suppresses the survival and proliferation of cervical cancer cells","volume":"11","author":"She","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_33","first-page":"5799","article-title":"DNMTs inhibitor SGI-1027 induces apoptosis in Huh7 human hepatocellular carcinoma cells","volume":"16","author":"Sun","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/S2213-2600(18)30284-4","article-title":"Epigenetic prediction of response to anti-PD-1 treatment in non-small-cell lung cancer: A multicentre, retrospective analysis","volume":"6","author":"Duruisseaux","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref_35","first-page":"150","article-title":"DNA methylation as predictive marker of response to immunotherapy?","volume":"14","author":"Heller","year":"2021","journal-title":"Memo-Mag. Eur. Med. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Sigin, V.O., Kalinkin, A.I., Kuznetsova, E.B., Simonova, O.A., Chesnokova, G.G., Litviakov, N.V., Slonimskaya, E.M., Tsyganov, M.M., Ibragimova, M.K., and Volodin, I.V. (2020). DNA methylation markers panel can improve prediction of response to neoadjuvant chemotherapy in luminal B breast cancer. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-66197-1"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e003420","DOI":"10.1136\/jitc-2021-003420","article-title":"DNA methylation profiles differ in responders versus non-responders to anti-PD-1 immune checkpoint inhibitors in patients with advanced and metastatic head and neck squamous cell carcinoma","volume":"10","author":"Starzer","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-018-1236-z","article-title":"Epigenetic silencing of ZNF132 mediated by methylation-sensitive Sp1 binding promotes cancer progression in esophageal squamous cell carcinoma","volume":"10","author":"Jiang","year":"2019","journal-title":"Cell Death Dis."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/3\/281\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:04:00Z","timestamp":1760105040000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/3\/281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,23]]},"references-count":38,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["genes15030281"],"URL":"https:\/\/doi.org\/10.3390\/genes15030281","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,23]]}}}