Possible Role of miR-375-3p in Cervical Lymph Node Metastasis of Oral Squamous Cell Carcinoma

Simple Summary We focused on microRNAs (miRNAs) and investigated their usefulness as predictive markers for latent cervical lymph node metastasis (LNM) in early oral squamous cell carcinoma (OSCC). In miRNA microarray analysis, RT quantitative PCR, and digital PCR, the expression levels of miR-375-3p were significantly reduced in primary OSCC tissues with latent cervical LNM. Next, we examined the effects of miR-375-3p mimics on the growth and migration of four human OSCC cell lines that do not express miR-375-3p. When miR-375-3p mimics were introduced into human OSCC cells, cell proliferation and migration were significantly suppressed. Furthermore, a microarray and the Ingenuity Pathway Analysis miRNA target filter found 37 target gene candidates of miR-375-3p. Of these genes, the knockdown of CEPT1 and TIMM8A expression significantly inhibited the migration of human OSCC cells, similar to miR-375-3p mimics. The downregulation of miR-375-3p could promote cervical LNM by enhancing cell proliferation and migration in OSCC.Abstract No clinically useful predictors of latent cervical lymph node metastasis (LNM) in early oral squamous cell carcinoma (OSCC) are available. In this study, we focused on the microRNAs (miRNAs) involved in the expression of numerous genes and explored those associated with latent cervical LNM in early OSCC (eOSCC). First, microarray and RT-PCR analyses revealed a significant downregulation of miR-375-3p expression in primary eOSCC tissues with latent cervical LNM. Next, we examined the effects of miR-375-3p mimics on the growth and migration of four human OSCC cell lines that do not express miR-375-3p. The overexpression of miR-375-3p significantly suppressed the cell proliferation and migration of human OSCC cells in vitro. Furthermore, miR-375-3p mimics markedly inhibited the subcutaneously xenografted human OSCC tumors. Finally, we found the genes involved in the PI3K-AKT pathway and cell migration as target gene candidates of miR-375-3p in human OSCC cells. These findings suggest that miR-375-3p functions as a tumor suppressive-miRNA in OSCC and may serve as a potential biomarker for the prediction of latent cervical LNM in eOSCC and a useful therapeutic target to suppress OSCC progression.