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Recent evidence suggests that microRNAs, particularly miR-1-3p, may regulate the molecular pathways associated with tumor invasion. This study aimed to investigate the functional role of miR-1-3p in OSCC invasion using integrated\n                      <jats:italic>in vitro<\/jats:italic>\n                      ,\n                      <jats:italic>in vivo<\/jats:italic>\n                      , and\n                      <jats:italic>ex vivo<\/jats:italic>\n                      approaches, and to evaluate its expression in tumors with varying depths of invasion (DOI).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>SCC-9 cells were transfected with miR-1-3p mimic and inhibitor. Invasion was assessed using transwell assays. Zebrafish xenografts were generated to evaluate tumor area, invasion depth, migration, and metastasis. Additionally, miR-1-3p expression was quantified by RT-qPCR in 26 human OSCC samples stratified by different groups of DOI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      miR-1-3p inhibition significantly increased tumor cell invasion\n                      <jats:italic>in vitro<\/jats:italic>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.039) and resulted in larger, deeper, and more migratory tumors\n                      <jats:italic>in vivo<\/jats:italic>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). All\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments were performed in duplicate, which may limit the precision of quantitative estimates. Metastases were observed in 30.8% of larvae injected with miR-1-3p\u2013inhibited cells, representing a trend toward increased metastatic behavior (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.052). In human samples, miR-1-3p expression was significantly negatively correlated with DOI (Spearman\u2019s\n                      <jats:italic>R<\/jats:italic>\n                      = \u2212\u20090.435;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.030), and deeply invasive tumors exhibited lower expression levels (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.040).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This integrative analysis supports an association between miR-1-3p downregulation and increased invasive tumor behavior in OSCC across experimental models and human tumor samples. These findings provide preliminary translational evidence and support further investigation into the potential role of miR-1-3p as a biomarker in OSCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11033-026-11914-8","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T11:16:43Z","timestamp":1778757403000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["miR-1-3p downregulation drives tumor invasion in oral squamous cell carcinoma: insights from in vitro, in vivo, and ex vivo models"],"prefix":"10.1007","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7482-7516","authenticated-orcid":false,"given":"Jessica Boscariol","family":"da Silva","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8258-8642","authenticated-orcid":false,"given":"Jos\u00e9 Leonardo","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7281-4044","authenticated-orcid":false,"suffix":"Jr.","given":"Gilberto Mendes","family":"Menderico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7999-5818","authenticated-orcid":false,"given":"Laura","family":"Sichero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3080-9447","authenticated-orcid":false,"given":"Hernandes F.","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0481-156X","authenticated-orcid":false,"given":"Luiz Paulo","family":"Kowalski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5068-8208","authenticated-orcid":false,"given":"Leandro Luongo","family":"Matos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"11914_CR1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13027-016-0067-8","volume":"11","author":"JC Betiol","year":"2016","unstructured":"Betiol JC, Sichero L, Costa HOO, de Matos LL, Andreoli MA, Ferreira S et al (2016) Prevalence of human papillomavirus types and variants and p16(INK4a) expression in head and neck squamous cells carcinomas in Sao Paulo, Brazil. 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This study was approved by the Animal Ethics Committee (CEUA \u2013 protocol 1538\/2020). The\n                      ex vivo\n                      study was approved by the Institutional Ethics Committee under protocol number 228\/14 (CAAE 32884214.5.0000.0065).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All human participants provided written informed consent to participate in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All authors have read and approved the final manuscript and do not have any actual, potential, or apparent conflicts of interest concerning the manuscript submitted for review.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that AI- and AI-assisted technologies in the writing process were not used for the preparation of this study.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Generative AI in scientific writing"}}],"article-number":"761"}}