miR-3928v is induced by HBx via NF-κB/EGR1 and contributes to hepatocellular carcinoma malignancy by down-regulating VDAC3
Open Access
- 29 January 2018
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Experimental & Clinical Cancer Research
- Vol. 37 (1), 1-12
- https://doi.org/10.1186/s13046-018-0681-y
Abstract
Background: Hepatitis B virus (HBV) plays a critical role in the tumorigenic behavior of human hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) have been reported to participate in HCC development via the regulation of their target genes. However, HBV-modulated miRNAs involved in tumorigenesis remain to be identified. Here, we found that a novel highly expressed miRNA, TLRC-m0008_3p (miR-3928v), may be an important factor that promotes the malignancy of HBV-related HCC. Methods: Solexa sequencing was applied to profile miRNAs, and RT-qPCR was used to identify and quantitate miRNAs. We studied miR-3928v function in HCC cell lines by MTT, colony formation, migration/invasion, and vascular mimicry (VM) assays in vitro and by a xenograft tumor model in vivo. Finally, we predicted and verified the target gene of miR-3928v by a reporter assay, studied the function of this target gene, and cloned the promoter of miR-3928v and the transcription factor for use in dual-luciferase reporter assays and EMSAs. Results: A variant of miR-3928 (miR-3928v) was identified and found to be highly expressed in HBV (+) HCC tissues. Voltage-dependent anion channel 3 (VDAC3) was validated as a target of miR-3928v and found to mediate the effects of miR-3928v in promoting HCC growth and migration/invasion. Furthermore, HBx protein increased early growth response 1 (EGR1) expression and facilitated its translocation into the nucleus to enhance miR-3928v promoter activity in an NF-kappa B signaling-dependent manner. Conclusions: miR-3928v is induced by HBx through the NF-kappa B/EGR1 signaling pathway and down-regulates the tumor suppressor gene VDAC3 to accelerate the progression of HCC.Keywords
Funding Information
- National Natural Science Foundation of China (91629302, 81572790, 31270818, 81602410)
- Natural Science Foundation of Tianjin City (12JCZDJC25100)
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