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Oncogene. 2019 Jan;38(3):406-420. doi: 10.1038/s41388-018-0440-8. Epub 2018 Aug 16.

KIFC1 regulated by miR-532-3p promotes epithelial-to-mesenchymal transition and metastasis of hepatocellular carcinoma via gankyrin/AKT signaling.

Author information

1
Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
2
Department of Head and Neck Surgery, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
3
Department of Gastrointestinal Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
4
Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China. mengxianzhi@sina.com.
5
Department of Head and Neck Surgery, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China. drzhangjiewu@sohu.com.
6
Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China. liulx@ems.hrbmu.edu.cn.

Abstract

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.

PMID:
30115976
PMCID:
PMC6336682
DOI:
10.1038/s41388-018-0440-8
[Indexed for MEDLINE]
Free PMC Article

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