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Biochim Biophys Acta Mol Cell Res. 2018 Jan;1865(1):1-11. doi: 10.1016/j.bbamcr.2017.09.020. Epub 2017 Oct 3.

Hepatitis B core protein promotes liver cancer metastasis through miR-382-5p/DLC-1 axis.

Author information

1
Central Laboratory, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250012, China. Electronic address: 318345812@qq.com.
2
Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Medicine, Jinan, Shandong 250012, China.
3
Center of Translational Medicine, Zibo Central Hospital, 54# Gongqingtuan Road, Zibo 255036, China.
4
Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan 250012, China.
5
Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Medicine, Jinan, Shandong 250012, China. Electronic address: liangxiaohong@sdu.edu.cn.

Abstract

The hepatitis B virus core protein (HBc), also named core antigen, is well-known for its key role in viral capsid formation and virus replication. Recently, studies showed that HBc has the potential to control cell biology activity by regulating host gene expression. Here, we utilized miRNA microarray to identify 24 upregulated miRNAs and 21 downregulated miRNAs in HBc-expressed HCC cells, which were involved in multiple biological processes, including cell motility. Consistently, the in vitro transwell assay and the in vivo tail-vein injection model showed HBc promotion on HCC metastasis. Further, the miRNA-target gene network analysis displayed that the deleted in liver cancer (DLC-1) gene, an important negative regulator for cell motility, was potentially targeted by several differentially expressed miRNAs in HBc-introduced cells. Introduction of miRNAs mimics or inhibitors and 3'UTR luciferase activity assay proved that miR-382-5p efficiently suppressed DLC-1 expression and its 3'-UTR luciferase reporter activity. Importantly, cotransfection of miR-382-5p mimics/inhibitors and the DLC-1 expression vector almost abrogated HBc promotion on cell motility, indicating that the miR-382-5p/DLC-1 axis is important for mediating HBc-enhanced HCC motility. Clinical HCC samples also showed a negative correlation between miR-382-5p and DLC-1 expression level. Furthermore, HBc-positive HCC tissues showed high miR-382-5p level and reduced DLC-1 expression. In conclusion, our findings revealed that HBc promoted HCC motility by regulating the miR-382-5p/DLC-1 axis, which might provide a novel target for clinical diagnosis and treatment.

KEYWORDS:

DLC-1; HBc; HCC; Motility; miR-382-5p

PMID:
28982593
DOI:
10.1016/j.bbamcr.2017.09.020
[Indexed for MEDLINE]
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