Cao He, Zheng Jing, Yao Yinan, Yang Qi, Yan Runlan, Sun Wenjia, Ruan Kexin, Zhou Jianya, Zhou Jianying
Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Department of Respiratory Disease, The First Affiliated Hospital of Jiaxing, Jiaxing University, Jiaxing 314000, China.
J Cancer. 2020 Sep 23;11(22):6663-6674. doi: 10.7150/jca.45962. eCollection 2020.
Lung cancer is the leading cause of cancer related death worldwide, with a continue-rising incidence. The proliferating cell nuclear antigen binding protein KIAA0101 is highly expressed in various types of cancer, including non-small cell lung cancer (NSCLC). However, its biological role and underlying mechanisms in NSCLC remains unclear. We downloaded KIAA0101 mRNA and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and verified the KIAA0101 expression by conducting experiments of immunochemistry (IHC), immunofluorescence (IF), quantitative real-time PCR (qRT-PCR) and western-blot. Functional experiments were performed to explore the biological roles and . The results showed that KIAA0101 was overexpressed in NSCLC tissues and cell lines. High KIAA0101 expression was associated with high T stage, nodal invasion, advanced tumor stage, and poor overall survival (<0.01). The receiver operating characteristic (ROC) curves showed that KIAA0101 could distinguish NSCLC from paired normal tissues with statistical significance (AUC=0.969, <0.001). The multivariate analysis revealed that KIAA0101 was an independent prognostic factor for overall survival (HR=1.249, 95% CI: 1.001-1.559, =0.049). Furthermore, KIAA0101 knockdown induced G1 phase cell cycle arrest and inhibited NSCLC cell proliferation and migration. We also found that the depletion of KIAA0101 decreased tumor volume in nude mice. In summary, our findings suggested that KIAA0101 was a reliable diagnostic and prognostic factor in NSCLC, with potential to be a promising treatment target.
肺癌是全球癌症相关死亡的主要原因，其发病率持续上升。增殖细胞核抗原结合蛋白KIAA0101在包括非小细胞肺癌（NSCLC）在内的多种癌症中高表达。然而，其在NSCLC中的生物学作用及潜在机制仍不清楚。我们从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）下载了KIAA0101 mRNA和临床数据，并通过免疫组织化学（IHC）、免疫荧光（IF）、定量实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹实验验证了KIAA0101的表达。进行功能实验以探索其生物学作用。结果显示，KIAA0101在NSCLC组织和细胞系中过表达。高KIAA0101表达与高T分期、淋巴结浸润、肿瘤晚期及总生存期差相关（<0.01）。受试者工作特征（ROC）曲线显示，KIAA0101能够在统计学上显著地区分NSCLC与配对的正常组织（AUC = 0.969，<0.001）。多因素分析显示，KIAA0101是总生存期的独立预后因素（HR = 1.249，95% CI：1.001 - 1.559，= 0.049）。此外，敲低KIAA0101可诱导G1期细胞周期阻滞并抑制NSCLC细胞增殖和迁移。我们还发现，敲低KIAA0101可减小裸鼠肿瘤体积。总之，我们的研究结果表明，KIAA0101是NSCLC中一个可靠的诊断和预后因素，有潜力成为一个有前景的治疗靶点。
