摘要
Zinc finger and BTB domain containing 16(ZBTB16),亦称早幼粒细胞白血病锌指蛋白(promyelocytic leukemia zinc finger,PLZF),作为一种转录抑制因子在调控细胞周期、增殖、分化和凋亡等多种功能中发挥重要作用,但其在肝癌组织中的表达情况及调控作用仍研究得较少。本研究利用GEPIA在线对TCGA肿瘤组织数据库和GTEx正常组织数据库中369例人肝癌组织和160例人正常肝组织中ZBTB16的表达进行生物信息学分析。结果发现,ZBTB16在人肝癌组织中表达显著下调;实时荧光定量PCR和Western blotting发现肝癌临床样本和肝癌细胞系中ZBTB16 mRNA和蛋白质水平均明显下调;GEPIA在线分析示ZBTB16表达水平与肝癌患者的生存率呈正相关。利用Ad-ZBTB16腺病毒在肝癌细胞系HepG2中过表达ZBTB16能显著抑制细胞的增殖、迁移和侵袭能力。进一步机制研究表明,过表达ZBTB16能显著抑制JAK2和STAT3的磷酸化水平。以上结果表明,提高ZBTB16的表达或可作为肝癌治疗的靶点。
Zinc finger and BTB domain containing 16(ZBTB16),also known as promyelocytic leukemia zinc finger(PLZF),acts as a transcriptional repressor in regulating cell cycle,proliferation,differentiation and apoptosis.However,there are few studies on its expression pattern and function in hepatocellular carcinoma(HCC).The expression pattern of ZBTB16 in the 369 HCC tissues from TCGA database and 160 normal liver tissues from GTEx database was analyzed in this study.Compared to normal liver tissues,the expression of ZBTB16 was found to be significantly down-regulated in HCC tissues.Western blotting and Real-time quantitative PCR analysis confirmed the down-regulation of ZBTB16 in HCC clinical samples and HCC cell lines.The expression level of ZBTB16 was positively correlated with the overall survival of HCC patients.Overexpression of ZBTB16 in the HCC cell line HepG2 by Ad-ZBTB16 significantly inhibited cell proliferation,migration and invasion.Further mechanistic studies showed that overexpression of ZBTB16 significantly inhibited the phosphorylation levels of JAK2 and STAT3.These results suggest that increasing the expression of ZBTB16 may serve as a target for future HCC treatment.
作者
于玲
于敏
YU Ling;YU Min(Research and Development Department,3D Medicines(Beijing)Co.Ltd,Beijing100176,China;Department of Cardiology,the Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,China)
出处
《现代免疫学》
CAS
CSCD
北大核心
2020年第1期16-21,共6页
Current Immunology
关键词
肝癌
ZBTB16
增殖
迁移
侵袭
hepatocellular carcinoma
zinc finger and BTB domain containing 16
proliferation
migration
invasion
