miR-3928v is induced by HBx via NF-κB/EGR1 and contributes to hepatocellular carcinoma malignancy by down-regulating VDAC3.

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-κB signaling-dependent manner.

CONCLUSIONS:

miR-3928v is induced by HBx through the NF-κB/EGR1 signaling pathway and down-regulates the tumor suppressor gene VDAC3 to accelerate the progression of HCC.

• Authors: Qiaoge Zhang, Ge Song, Lili Yao, Yankun Liu, Min Liu, Shengping Li, Hua Tang
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 37 Issue 1 Pg. 14 (Jan 29 2018) ISSN: 1756-9966 [Electronic] England
• PMID: 29378599 (Publication Type: Journal Article, Retracted Publication)

Chemical References

• 3' Untranslated Regions
• Early Growth Response Protein 1
• MicroRNAs
• Mitochondrial Membrane Transport Proteins
• NF-kappa B
• Trans-Activators
• VDAC3 protein, human
• Viral Regulatory and Accessory Proteins
• Voltage-Dependent Anion Channels
• hepatitis B virus X protein

Topics

• 3' Untranslated Regions
• Animals
• Carcinoma, Hepatocellular (etiology, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation
• Disease Models, Animal
• Early Growth Response Protein 1 (metabolism)
• Gene Expression Regulation, Neoplastic
• Hep G2 Cells
• Humans
• Liver Neoplasms (etiology, metabolism, pathology)
• Mice
• MicroRNAs (chemistry, genetics)
• Mitochondrial Membrane Transport Proteins (genetics, metabolism)
• NF-kappa B (metabolism)
• Nucleic Acid Conformation
• Oncogenes
• RNA Interference
• Signal Transduction
• Trans-Activators (metabolism)
• Viral Regulatory and Accessory Proteins
• Voltage-Dependent Anion Channels (genetics, metabolism)
• Xenograft Model Antitumor Assays