Department of Hepatobiliary Surgery, Aerospace Center Hospital , Beijing , China.
Department of Hepatobiliary Surgery, Peking University People's Hospital , Beijing , China.
Cancer Biol Ther. 2019;20(9):1223-1233. doi: 10.1080/15384047.2019.1617562. Epub 2019 May 27.
The aim of this study was to investigate the effects and mechanisms of hematopoietic-substrate-1-associated protein X-1 (HAX-1) on liver cancer cells. Information on HAX-1 from liver cancer patients was analyzed by the Cancer Genome Atlas (TCGA) program. Cell migration and invasion abilities were respectively tested by scratch assay and transwell assay. Tube formation assay was applied to detect angiogenesis protein and mRNA was determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. We found that the median month survival of HAX-1 overexpressing liver cancer patients was shorter than that of HAX-1 normal liver cancer patients. HAX-1 was overexpressed in liver cancer tissues and cells, and HAX-1 overexpression promoted the liver cancer cells growth, migration, and invasion, whereas silencing HAX-1 produced the opposite results. Inhibition of Akt by LY294002 reversed the migration and invasion abilities of liver cancer cells, and inhibited the ability of cells growth and angiogenesis. Silencing PIK3CA enhanced the inhibitory effects of HAX-1 silencing on the viability, migration, and invasion of liver cancer cells. HAX-1 affected liver cancer cells metastasis and angiogenesis by affecting Akt phosphorylation and FOXO3A expression.
本研究旨在探讨造血基质蛋白 1 相关蛋白 X-1（HAX-1）对肝癌细胞的作用及其机制。利用癌症基因组图谱（TCGA）程序分析肝癌患者的 HAX-1 信息。通过划痕实验和 Transwell 实验分别检测细胞迁移和侵袭能力。采用管形成实验检测血管生成蛋白，采用定量实时聚合酶链反应（qRT-PCR）和 Western blot 检测 mRNA。结果发现，HAX-1 高表达肝癌患者的中位月生存率短于 HAX-1 正常肝癌患者。HAX-1 在肝癌组织和细胞中高表达，HAX-1 过表达促进肝癌细胞生长、迁移和侵袭，而沉默 HAX-1 则产生相反的结果。LY294002 抑制 Akt 逆转了肝癌细胞的迁移和侵袭能力，并抑制了细胞生长和血管生成的能力。沉默 PIK3CA 增强了 HAX-1 沉默对肝癌细胞活力、迁移和侵袭的抑制作用。HAX-1 通过影响 Akt 磷酸化和 FOXO3A 表达影响肝癌细胞的转移和血管生成。
