Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers and the second leading cause of cancer related death worldwide. ZNF545 is located in the chromosome 19q13.13, which is frequent loss of heterozygosity in human astrocytoma. Methylation of ZNF545 was found frequently in a few kinds of cancers. While the function of ZNF545 in human HCC remains unclear. The purpose of this study is to explore the function and mechanism of ZNF545 in human HCC. Restoration of ZNF545 expression suppressed cell proliferation, migration and invasion, induced G1/S arrest and apoptosis in SNU449 and Huh7 cells. Further study suggested that ZNF545 suppressed HCC cell growth by inhibiting NF-kB signaling. These results were further validated by siRNA knocking down technique in ZNF545 highly expressed HXBF344 cells. In vivo, ZNF545 suppressed tumor growth in SNU449 cell xenograft mice. In conclusion, ZNF545 suppresses human HCC growth by inhibiting NF-kB signaling.

Highlights

  • Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the second cause of cancer-associated death [1, 2]

  • We found Zinc-finger protein 545 (ZNF545) was frequently methylated in human HCC and the expression of ZNF545 was regulated by promoter region methylation [14]

  • These results demonstrate that ZNF545 suppresses the proliferation of HCC cells

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the second cause of cancer-associated death [1, 2]. Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection constitutes the most important cause of HCC. Alcohol abuse and dietary exposure to aflatoxin B contamination are involved in HCC carcinogenesis[3]. Only four genes (TP53, CTNNB1, ARID1A and AXIN1) were found mutated more than 10% in HCC [3, 4]. Aberrant epigenetic changes were found frequently in human HCC. DNA methylation was found involved in various cancerrelated signaling pathways, including Wnt, p53, and TGF-β signaling [5,6,7,8,9]

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