Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Int J Oncol. 2018 Feb;52(2):536-546. doi: 10.3892/ijo.2017.4224. Epub 2017 Dec 11.
MicroRNAs (miRNAs or miRs) have been shown to regulate hepatocellular carcinoma (HCC) metastasis. In the present study, we focused on the functions of miR-1271 in HCC metastasis. The downregulation of miR-1271 was found to be associated with to venous infiltration, an advanced TNM stage (III+IV stage) and a shorter survival time. Our in vitro and in vivo data demonstrated that miR-1271 prevented HCC cell migration and invasion, as well as the formation of lung metastatic clusters. In addition, miR-1271 was demonstrated to markedly inhibit the epithelial-mesenchymal transition (EMT) of HCC cells. Importantly, protein tyrosine phosphatase type IVA member 1 (PTP4A1) was identified as a direct downstream target of miR-1271 in HCC. Furthermore, we confirmed that the phosphorylation of c-Src at Tyr416 mediated by PTP4A1 was a potential anti-HCC mechanism of action of miR-1271. On the whole, our data indicate that miR-1271 inhibits HCC metastasis by targeting the PTP4A1/c-Src signaling pathway and may serve as a prospective cancer therapeutic target for HCC.
MicroRNAs (miRNAs 或 miRs) 已被证明可调节肝细胞癌 (HCC) 转移。在本研究中，我们专注于 miR-1271 在 HCC 转移中的功能。下调 miR-1271 与静脉浸润、晚期 TNM 分期 (III+IV 期) 和较短的生存时间有关。我们的体外和体内数据表明，miR-1271 可防止 HCC 细胞迁移和侵袭，以及肺转移簇的形成。此外，miR-1271 明显抑制了 HCC 细胞的上皮-间充质转化 (EMT)。重要的是，蛋白酪氨酸磷酸酶 IVA 成员 1 (PTP4A1) 被鉴定为 HCC 中 miR-1271 的直接下游靶标。此外，我们证实了 PTP4A1 通过 Tyr416 介导的 c-Src 磷酸化是 miR-1271 发挥潜在 HCC 作用机制的一种方式。总的来说，我们的数据表明，miR-1271 通过靶向 PTP4A1/c-Src 信号通路抑制 HCC 转移，可能成为 HCC 的有前途的癌症治疗靶点。
