Wang Di, Xiao Jiayu, Du Yang, Zhang Li, Qin Xuzhen
Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Biomedicines. 2024 Sep 2;12(9):1981. doi: 10.3390/biomedicines12091981.
DNAJB6, a major member of the DNAJ/HSP40 family, plays an important role in tumor development. We explored the effect of DNAJB6 expression on the prognosis of patients and its biological role in lung adenocarcinoma (LUAD). mRNA and clinical data were obtained from The Cancer Genome Atlas (TCGA). Enriched pathways were determined by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A nomogram incorporating DNAJB6 and three clinical features was constructed to predict the survival rate. DNAJB6 expression and function in LUAD were explored using immunohistochemistry, Western blotting, proliferation, cell cycle analysis, RNA sequencing, and xenograft tumor assays. mRNA levels were elevated in the LUAD-TCGA dataset. DNAJB6 protein levels were higher in LUAD tumor tissues than in normal tissues. A high DNAJB6 level was an independent risk factor for poor prognosis in patients with LUAD. The proportion of tumor-infiltrating immune cells significantly differed between high and low expression. DNAJB6 was associated with cell cycle pathways; therefore, its knockdown induced G2/M cell cycle arrest and inhibited LUAD cell proliferation. This is the first report of the DNAJB6 requirement for LUAD cell proliferation and its potentially crucial role in LUAD prognosis.
DNAJB6是DNAJ/HSP40家族的主要成员，在肿瘤发展中发挥重要作用。我们探讨了DNAJB6表达对患者预后的影响及其在肺腺癌（LUAD）中的生物学作用。从癌症基因组图谱（TCGA）获取mRNA和临床数据。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析确定富集途径。构建了一个包含DNAJB6和三个临床特征的列线图来预测生存率。使用免疫组织化学、蛋白质免疫印迹法、增殖实验、细胞周期分析、RNA测序和异种移植肿瘤实验来探究DNAJB6在LUAD中的表达和功能。在LUAD-TCGA数据集中mRNA水平升高。LUAD肿瘤组织中的DNAJB6蛋白水平高于正常组织。高DNAJB6水平是LUAD患者预后不良的独立危险因素。高表达和低表达之间肿瘤浸润免疫细胞的比例存在显著差异。DNAJB6与细胞周期途径相关；因此，其敲低诱导G2/M期细胞周期阻滞并抑制LUAD细胞增殖。这是关于DNAJB6对LUAD细胞增殖的需求及其在LUAD预后中潜在关键作用的首次报道。
