4.6 Article

MicroRNA-769-3p Acts as a Prognostic Factor in Oral Squamous Cell Cancer by Modulating Stromal Genes

Journal

CANCERS
Volume 14, Issue 18, Pages -

Publisher

MDPI
DOI: 10.3390/cancers14184373

Keywords

miR-769; head and neck neoplasm; stroma; tumor-suppressive; EMT

Categories

Funding

  1. Catholic University of Korea Uijeongbu St. Mary's Hospital Clinical Research Laboratory Foundation [UJBCRL201840]
  2. Catholic University of Korea [5-2020-D0403-00001]
  3. Basic Science Research Program through the National Research Foundation - Ministry of Education [NRF-2020R1I1A1A01066968]

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This study found that miR-769-3p is overexpressed in the stromal cells of oral squamous cell carcinoma and inhibits the proliferation, migration, and invasion of cancer cells. miR-769-3p may serve as a potential biomarker of the miRNA phenotype in oral squamous cell carcinoma.
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. 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.

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