Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. The poor survival may be due to a high proportions of tumor recurrence and metastasis. Kinesin family member C1 (KIFC1) is highly expressed in a variety of neoplasms and is a potential marker for non-small cell lung cancer or ovarian adenocarcinoma metastasis. Nevertheless, the role of KIFC1 in HCC metastasis remains obscure. We investigated this in the present study using HCC cell lines and clinical specimens. Our results indicated that increased levels of KIFC1 were associated with poor prognosis and metastasis in HCC. In addition, KIFC1 induced epithelial-to-mesenchymal transition (EMT) and HCC metastasis both in vitro and in vivo. This tumorigenic effect depended on gankyrin; inhibiting gankyrin activity reversed EMT via activation of protein kinase B (AKT)/Twist family BHLH transcription factor 1 (AKT/TWIST1). We also found that KIFC1 was directly regulated by the microRNA miR-532-3p, whose downregulation was associated with metastatic progression in HCC. These results denote that a decrease in miR-532-3p levels results in increased KIFC1 expression in HCC, leading to metastasis via activation of the gankyrin/AKT/TWIST1 signaling pathway.

中文翻译：

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由miR-532-3p调控的KIFC1通过gankyrin / AKT信号传导促进肝细胞癌的上皮向间充质转化和转移。

肝细胞癌（HCC）是全球最致命的癌症之一。不良的存活率可能是由于高比例的肿瘤复发和转移所致。驱动蛋白家族成员C1（KIFC1）在各种肿瘤中高表达，并且是非小细胞肺癌或卵巢腺癌转移的潜在标志物。然而，KIFC1在肝癌转移中的作用仍然不清楚。我们在本研究中使用HCC细胞系和临床标本对此进行了调查。我们的结果表明，KIFC1水平升高与肝癌的不良预后和转移有关。此外，KIFC1在体外和体内均可诱导上皮-间充质转化（EMT）和HCC转移。这种致瘤作用取决于gankyrin。抑制gankyrin活性可通过激活蛋白激酶B（AKT）/ Twist家族BHLH转录因子1（AKT / TWIST1）来逆转EMT。我们还发现KIFC1直接受microRNA miR-532-3p调控，其下调与HCC的转移进程有关。这些结果表明，miR-532-3p水平的降低导致肝癌中KIFC1表达增加，并通过激活gankyrin / AKT / TWIST1信号通路而导致转移。