{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:20:23Z","timestamp":1781101223992,"version":"3.54.1"},"reference-count":43,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University Research Institute of Maternal and Child Health and Precision Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Oral squamous cell carcinoma (OSCC) is a highly aggressive neoplasm characterized by grim survival outcomes, despite significant therapeutic advances. Mortality rates (up to 70%) have remained unaltered for decades, predominantly due to profound diagnostic delays. These derive from the asymptomatic nature of the early stages of oral carcinogenesis and the emergence of dysplastic areas in previously benign lesions, acting as the bridge to malignant transformation. Hence, the establishment of reliable salivary biomarkers is crucial for non-invasive OSCC detection, even from the premalignant stage of dysplasia. Based on our previous bioinformatic research identifying stage-specific miRNAs throughout OSCC progression, which yielded miR-34a-5p as the most significant, we aimed to experimentally investigate its role in oral oncogenesis and explore its stage-reflecting biomarker potential for liquid biopsy. Methods: The expression of miR-34a was evaluated using quantitative real-time PCR in saliva samples from 9 patients with oral premalignant dysplastic lesions, 10 patients with OSCC and 10 healthy controls. The diagnostic accuracy of miR-34a expression profiles was assessed using ROC-curve analyses. Results: The expression of salivary miR-34a differed significantly across the studied groups, demonstrating a steep decrease in the presence of epithelial premalignant dysplasia, significant upregulation in OSCC and intermediate levels in normal oral mucosa (p &lt; 0.001). The ROC results indicate strong diagnostic performance for the detection of oral dysplasia (AUC = 0.93; p &lt; 0.001), OSCC (AUC = 0.77; p = 0.01) and excellent accuracy for the discrimination between premalignant and OSCC lesions (AUC = 0.98; p &lt; 0.001). Conclusions: Our findings reveal a state-dependent dysregulation of miR-34a in oral carcinogenesis, suggesting its complex role as a pathogenetic agent that allows for malignant transformation through its diminished expression, and as a secondary reactive mechanism attempting to suppress tumor development. Salivary miR-34a holds great, stage-specific diagnostic potential, thereby reflecting the health state of oral mucosa in real time.<\/jats:p>","DOI":"10.3390\/genes16121495","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T13:32:37Z","timestamp":1765805557000},"page":"1495","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Salivary miR-34a Exhibits State-Dependent Dysregulation Across Normal Oral Mucosa, Premalignant Lesions and Oral Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2561-9595","authenticated-orcid":false,"given":"Iphigenia","family":"Gintoni","sequence":"first","affiliation":[{"name":"Unit of Orofacial Genetics, 1st Department of Pediatrics, School of Medicine, National Kapodistrian University of Athens, \u201cAghia Sophia\u201d Children\u2019s Hospital, 115 27 Athens, Greece"},{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, National Kapodistrian University of Athens, Choremion Laboratory, \u201cAghia Sophia\u201d Children\u2019s Hospital, 115 27 Athens, Greece"},{"name":"Department of Oral and Maxillofacial Surgery, School of Medicine, National Kapodistrian University of Athens, Attikon Hospital, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6102-2551","authenticated-orcid":false,"given":"Stavros","family":"Vassiliou","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Medicine, National Kapodistrian University of Athens, Attikon Hospital, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myrto","family":"Kardara Bellou","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Medicine, National Kapodistrian University of Athens, Attikon Hospital, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Balakas","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Medicine, National Kapodistrian University of Athens, Attikon Hospital, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Lefantzis","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Medicine, National Kapodistrian University of Athens, Attikon Hospital, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4033-1181","authenticated-orcid":false,"given":"Veronica","family":"Papakosta","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Medicine, National Kapodistrian University of Athens, Attikon Hospital, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3098-5264","authenticated-orcid":false,"given":"George P.","family":"Chrousos","sequence":"additional","affiliation":[{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, National Kapodistrian University of Athens, Choremion Laboratory, \u201cAghia Sophia\u201d Children\u2019s Hospital, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6695-186X","authenticated-orcid":false,"given":"Christos","family":"Yapijakis","sequence":"additional","affiliation":[{"name":"Unit of Orofacial Genetics, 1st Department of Pediatrics, School of Medicine, National Kapodistrian University of Athens, \u201cAghia Sophia\u201d Children\u2019s Hospital, 115 27 Athens, Greece"},{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, National Kapodistrian University of Athens, Choremion Laboratory, \u201cAghia Sophia\u201d Children\u2019s Hospital, 115 27 Athens, Greece"},{"name":"Department of Oral and Maxillofacial Surgery, School of Medicine, National Kapodistrian University of Athens, Attikon Hospital, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e71266","DOI":"10.1002\/cam4.71266","article-title":"Roles of MiR-181 Family Members in OSCC: Implications for Therapy and Diagnostics","volume":"14","author":"Aghiorghiesei","year":"2025","journal-title":"Cancer Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.amsu.2020.10.029","article-title":"Epidemiology and Pathology of Oral Squamous Cell Carcinoma in a Multi-Ethnic Population: Retrospective Study of 154 Cases over 7 Years in Qatar","volume":"60","author":"Elaiwy","year":"2020","journal-title":"Ann. 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