Oral squamous cell carcinoma (OSCC) is a common malignant cancer with unfavorable prognosis, and the epithelial‐to‐mesenchymal transition (EMT) is a critical contributor to OSCC metastasis. Recently, we have shown that sirtuin 7 (Sirt7) is associated with EMT and OSCC metastasis by acetylating small mother against decapentaplegic 4 (Smad4). Nonetheless, the mechanism of Sirt7 downregulation in OSCC cells remains unknown. This study analyzed the potential microRNAs that were predicted to regulate Sirt7 expression by online databases. We identified miR‐770 as an upstream regulator of Sirt7 that targets its 3′‐untranslated region. The expression of miR‐770 was observed to be negatively correlated with the mRNA expression of Sirt7 in metastatic OSCC tumors, and higher miR‐770 expression was correlated with poorer OSCC patient survival. Our in vitro data indicated that miR‐770 promoted OSCC cell migration and invasion, and this process was dependent on Sirt7/Smad4 signaling. Furthermore, in vivo metastasis experiments indicated that miR‐770 overexpression led to more prominent OSCC metastasis and downregulated Sirt7 expression. Collectively, our results revealed a new role of Sirt7 downregulation in metastatic OSCC and suggested that miR‐770 is a potential target in counteracting OSCC metastasis.

中文翻译：

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MiR ‐770 通过调节 Sirt7/Smad4 通路促进口腔鳞状细胞癌的迁移和侵袭

口腔鳞状细胞癌（OSCC）是一种预后不良的常见恶性肿瘤，上皮间质转化（EMT）是导致口腔鳞状细胞癌转移的重要因素。最近，我们已经表明，sirtuin 7 (Sirt7) 通过乙酰化小母体对抗 decapentaplegic 4 (Smad4) 与 EMT 和 OSCC 转移有关。尽管如此，OSCC细胞中Sirt7下调的机制仍然未知。本研究分析了在线数据库预测的调节 Sirt7 表达的潜在 microRNA。我们将 miR-770 鉴定为 Sirt7 的上游调节因子，靶向其 3'-非翻译区。在转移性 OSCC 肿瘤中观察到 miR-770 的表达与 Sirt7 的 mRNA 表达呈负相关，较高的 miR-770 表达与较差的 OSCC 患者生存率相关。我们的体外数据表明 miR-770 促进 OSCC 细胞迁移和侵袭，而这一过程依赖于 Sirt7/Smad4 信号。此外，体内转移实验表明 miR-770 过表达导致更显着的 OSCC 转移和下调 Sirt7 表达。总的来说，我们的结果揭示了 Sirt7 下调在转移性 OSCC 中的新作用，并表明 miR-770 是对抗 OSCC 转移的潜在靶点。