Interleukin-34 mediated by hepatitis B virus X protein via CCAAT/enhancer-binding protein α contributes to the proliferation and migration of hepatoma cells.

Abstract

OBJECTIVES:

Interleukin-34 (IL-34) is associated with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). However, the role and associated mechanisms of IL-34 in HBV-related HCC remain unclear. In this study, the expression, biological function and associated mechanisms of IL-34 in HBV-related HCC cells were investigated.

METHODS:

IL-34 expression induced by HBV and HBV X (HBX) gene was measured in hepatoma cells. The role of CCAAT/enhancer-binding protein α (CEBP/α) in HBX-induced IL-34 expression was examined. The signal pathways involved in the expression of CEBP/α and IL-34 induced by HBX were assessed. The role of IL-34 in the proliferation and migration of HCC cells, and related mechanisms were explored.

RESULTS:

Dependent on HBX, HBV increased IL-34 expression in hepatoma cells, and HBX upregulated and interacted with CEBP/α to enhance the activity of IL-34 promoters. CEBP/α mediated by HBX was associated with the activation of PI3-K and NF-κB pathways to promote IL-34 expression. Via CSF1-R and CD138, IL-34 promoted the proliferation and migration of hepatoma cells, and contributed to the activation of ERK and STAT3 pathways and the upregulation of Bcl-xl and c-Myc mediated by HBX.

CONCLUSION:

We demonstrate that IL-34 contributes to HBX-mediated functional abnormality of HCC cells and provides a novel insight into the molecular mechanism of carcinogenesis mediated by HBX.

• Authors: Fanyun Kong, Kai Zhou, Ting Zhu, Qi Lian, Yukai Tao, Nan Li, Tao Tu, Yanwei Bi, Xiaoying Yang, Xiucheng Pan, Shibao Li, Hongjuan You, Kuiyang Zheng, Renxian Tang
• Journal: Cell proliferation (Cell Prolif) Vol. 52 Issue 6 Pg. e12703 (Nov 2019) ISSN: 1365-2184 [Electronic] England
• PMID: 31621133 (Publication Type: Journal Article)
• Copyright: © 2019 The Authors. Cell Proliferation published by John Wiley & Sons Ltd.

Chemical References

• CCAAT-Enhancer-Binding Protein-alpha
• IL34 protein, human
• Interleukins
• Trans-Activators
• Viral Regulatory and Accessory Proteins
• hepatitis B virus X protein

Topics

• CCAAT-Enhancer-Binding Protein-alpha (metabolism)
• Carcinoma, Hepatocellular (genetics)
• Cell Line, Tumor
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Gene Expression Regulation, Neoplastic
• Hepatitis B
• Humans
• Interleukins (metabolism)
• Liver Neoplasms (genetics)
• Trans-Activators (metabolism)
• Viral Regulatory and Accessory Proteins