Yang Weili, Yang Shuai, Zhang Meiying, Gao Dan, He Tao, Guo Mingzhou
Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, China.
Medical College of NanKai University, Tianjin, China.
Genes Cancer. 2017 Mar;8(3-4):528-535. doi: 10.18632/genesandcancer.137.
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.
肝细胞癌（HCC）是最常见的癌症之一，也是全球癌症相关死亡的第二大主要原因。ZNF545位于19号染色体q13.13区域，在人类星形细胞瘤中该区域常发生杂合性缺失。在几种癌症中经常发现ZNF545的甲基化。然而，ZNF545在人类肝癌中的功能尚不清楚。本研究的目的是探讨ZNF545在人类肝癌中的功能及机制。ZNF545表达的恢复抑制了SNU449和Huh7细胞的增殖、迁移和侵袭，诱导了G1/S期阻滞和凋亡。进一步研究表明，ZNF545通过抑制NF-κB信号通路抑制肝癌细胞生长。这些结果在ZNF545高表达的HXBF344细胞中通过siRNA敲低技术得到了进一步验证。在体内，ZNF545抑制了SNU449细胞异种移植小鼠的肿瘤生长。总之，ZNF545通过抑制NF-κB信号通路抑制人类肝癌生长。
