LAUSR

Simple Summary Based on a recent report, miRNA expression profiles represent the head and neck squamous cell carcinoma (HNSCC) subtype (epithelial or stromal), owing to the ability of miRNAs to regulate developmental growth and differentiation programs in epithelial cells. The current study aimed to investigate the expression and function of miR-769-3p in the stromal phenotype of oral squamous cell cancer (OSCC). Our results showed that miR-769-3p is overexpressed in fibroblast-like cells within the stroma around tumor tissues. miR-769-3p overexpression inhibited the proliferation, migration, and invasion of OSCC cells. RNA sequencing revealed a tumor-suppressive role of miR-769-3p by modulating stromal gene expression, such as interferon-gamma-related genes and MYC target gene sets. miR-769-3p may be a potential biomarker of the miRNA phenotype in OSCC patients. These findings indicate that miR-769-3p plays a crucial role as a potential biomarker of the miRNA phenotype in OSCC patients. Abstract miR-769-3p expression is suppressed in the stromal subtype of head and neck squamous cell carcinoma (HNSCC); however, its role in stromal HNSCC has not been fully elucidated. To investigate the biological relevance of miR-769-3p in the stromal phenotype, we established oral squamous cell cancer (OSCC) cell lines, namely CAL27, HSC3, and YD8, overexpressing miR-769-3p. miR-769-3p expression was positively and negatively correlated with interferon-gamma-related genes and MYC target gene sets, respectively. miR-769-3p decreased OSCC cell migration and invasion as well as mesenchymal marker expression and increased epithelial marker expression. Moreover, miR-769-3p enhanced OSCC cell sensitivity to 5-fluorouracil. High miR-769-3p expression was associated with good prognosis of HNSCC patients. Collectively, these results suggest that miR-769-3p suppression enhances stromal gene expression and promotes the epithelial-to-mesenchymal transition. Therefore, miR-769-3p may be a potential biomarker of the miRNA phenotype in OSCC patients.