KIFC1 regulated by miR-532-3p promotes epithelial-to-mesenchymal transition and metastasis of hepatocellular carcinoma via gankyrin/AKT signaling.
KIFC1 regulated by miR-532-3p promotes epithelial-to-mesenchymal transition and metastasis of hepatocellular carcinoma via gankyrin/AKT signaling.
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miR-532-3p调控的KIFC1通过gankyrin/AKT信号促进肝细胞癌上皮间质转化和转移
DOI：
10.1038/s41388-018-0440-8
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发表时间：
2019-01
期刊：
影响因子：
8
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Han J;Wang F;Lan Y;Wang J;Nie C;Liang Y;Song R;Zheng T;Pan S;Pei T;Xie C;Yang G;Liu X;Zhu M;Wang Y;Liu Y;Meng F;Cui Y;Zhang B;Liu Y;Meng X;Zhang J;Liu L
肝细胞癌（HCC）是世界上最致命的癌症之一。生存率低可能是由于高比例的肿瘤复发和转移。驱动蛋白家族成员C1（KIFC 1）在多种肿瘤中高度表达，是非小细胞肺癌或卵巢腺癌转移的潜在标志物。然而，KIFC 1在HCC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研究。我们的研究结果表明，KIFC 1水平的升高与肝癌的预后不良和转移有关。此外，KIFC 1在体外和体内均诱导上皮向间充质转化（EMT）和HCC转移。这种致瘤作用依赖于Gankyrin;抑制Gankyrin活性通过激活蛋白激酶B（AKT）/Twist家族BHLH转录因子1（AKT/TWIST 1）逆转EMT。我们还发现KIFC 1直接受microRNA miR-532- 3 p的调节，其下调与HCC的转移进展相关。这些结果表明，miR-532- 3 p水平的降低导致HCC中KIFC 1表达增加，从而通过gankyrin/AKT/TWIST 1信号通路的激活导致转移。
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.
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影响因子：
2.8
作者：
Wang, Wu-ping;Yan, Xiao-long;Li, Xiao-Fei
通讯作者：
Li, Xiao-Fei
影响因子：
29.4
作者：
Serper M;Taddei TH;Mehta R;D'Addeo K;Dai F;Aytaman A;Baytarian M;Fox R;Hunt K;Goldberg DS;Valderrama A;Kaplan DE;VOCAL Study Group
通讯作者：
VOCAL Study Group
鉴定雌激素受体结合与乳腺癌的临床结局有关。
影响因子：
64.8
作者：
Ross-Innes, Caryn S.;Stark, Rory;Teschendorff, Andrew E.;Holmes, Kelly A.;Ali, H. Raza;Dunning, Mark J.;Brown, Gordon D.;Gojis, Ondrej;Ellis, Ian O.;Green, Andrew R.;Ali, Simak;Chin, Suet-Feung;Palmieri, Carlo;Caldas, Carlos;Carroll, Jason S.
通讯作者：
Carroll, Jason S.
影响因子：
64.5
作者：
Yang, J;Mani, SA;Weinberg, RA
通讯作者：
Weinberg, RA
影响因子：
9
作者：
Kanaan, Ziad;Roberts, Henry;Galandiuk, Susan
通讯作者：
Galandiuk, Susan