Abstract Aim Oral squamous cell carcinoma (OSCC) often presents as an invasive tumor with poor prognosis. 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 in vitro , in vivo , and ex vivo approaches, and to evaluate its expression in tumors with varying depths of invasion (DOI). Methods 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. Results miR-1-3p inhibition significantly increased tumor cell invasion in vitro ( P = 0.039) and resulted in larger, deeper, and more migratory tumors in vivo ( P < 0.05). All in vitro 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–inhibited cells, representing a trend toward increased metastatic behavior ( P = 0.052). In human samples, miR-1-3p expression was significantly negatively correlated with DOI (Spearman’s R = − 0.435; P = 0.030), and deeply invasive tumors exhibited lower expression levels ( P = 0.040). Conclusion 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.
Silva et al. (Thu,) studied this question.