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.
目前尚无临床可用的早期口腔鳞状细胞癌（OSCC）潜在颈部淋巴结转移（LNM）预测指标。本研究聚焦于参与多基因表达的微小RNA（miRNA），探索其与早期OSCC（eOSCC）潜在颈部LNM的关联。首先，通过微阵列和RT-PCR分析发现，在存在潜在颈部LNM的原发性eOSCC组织中，miR-375-3p表达显著下调。随后，我们在四种不表达miR-375-3p的人OSCC细胞系中检测了miR-375-3p模拟物对细胞生长和迁移的影响。过表达miR-375-3p能显著抑制人OSCC细胞的体外增殖和迁移能力。此外，miR-375-3p模拟物对皮下移植的人OSCC肿瘤生长具有明显抑制作用。最后，我们发现在人OSCC细胞中，参与PI3K-AKT通路及细胞迁移的相关基因可能是miR-375-3p的潜在靶基因。这些结果表明，miR-375-3p在OSCC中发挥肿瘤抑制性miRNA的功能，可能作为预测eOSCC潜在颈部LNM的潜在生物标志物，并成为抑制OSCC进展的有效治疗靶点。
Possible Role of miR-375-3p in Cervical Lymph Node Metastasis of Oral Squamous Cell Carcinoma
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