Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080, Guangdong, People's Republic of China.
Department of Organ Transplantation and General Surgery, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People's Republic of China.
J Cancer Res Clin Oncol. 2019 Mar;145(3):661-673. doi: 10.1007/s00432-018-2823-1. Epub 2019 Jan 14.
We aimed to analyze the expression of ZWINT, NUSAP1, DLGAP5, and PRC1 in tumor tissues and adjacent tissues with public data.
The expression patterns of four genes were detected in cancer tissues and adjacent tissues by qRT-PCR. The overall survival analysis was used to explore these genes in lung adenocarcinoma and squamous cell carcinoma patients. Knockdown assays were used to select the most suitable gene among these four genes. Cell function assays with the knockdown gene were conducted in A549 and NCL H226 cells. The role of the knockdown gene in lung cancer was dissected in a mice tumor model. Transcriptome sequencing analyses with the knockdown gene were analyzed.
Overexpression of these genes was significantly detected in cancer tissues (P < 0.01). Overall survival revealed that high expression of these genes is closely related with poor prognosis of lung adenocarcinoma patients (P < 0.05). Knockdown of ZWINT reduced proliferation in NCI H226 and A549 cells (P < 0.05). Knockdown also inhibited cell migration, invasion, apoptosis, and colony formation (P < 0.05). ZWINT knockdown reduced tumor volume (P < 0.05). Transcriptome sequencing of ZWINT knockdown-treated A549 and NCI H226 cells indicated that 100 and 426 differentially expressed genes were obtained, respectively. Gene ontology analysis suggested that binding, biological regulation, and multicellular organismal processes were the most enriched. KEGG analysis revealed that TNF, P53, and PI3K signal networks would be the most potential ZWINT-related pathways and were identified by Western blot analysis.
ZWINT may be a novel target for lung cancer therapy.
我们旨在通过公共数据分析 ZWINT、NUSAP1、DLGAP5 和 PRC1 在肿瘤组织和相邻组织中的表达。
通过 qRT-PCR 检测四种基因在癌组织和相邻组织中的表达模式。对肺腺癌和鳞癌患者进行总生存分析，以探讨这些基因的作用。通过敲低实验筛选这四个基因中最合适的基因。在 A549 和 NCL H226 细胞中进行敲低基因的细胞功能实验。在小鼠肿瘤模型中分析敲低基因在肺癌中的作用。分析敲低基因的转录组测序分析。
这些基因在癌组织中的表达明显上调（P<0.01）。总生存分析显示，这些基因的高表达与肺腺癌患者的不良预后密切相关（P<0.05）。ZWINT 的敲低降低了 NCI H226 和 A549 细胞的增殖（P<0.05）。敲低还抑制了细胞迁移、侵袭、凋亡和集落形成（P<0.05）。ZWINT 敲低降低了肿瘤体积（P<0.05）。对 ZWINT 敲低处理的 A549 和 NCI H226 细胞进行转录组测序分析，分别获得了 100 和 426 个差异表达基因。GO 分析表明，结合、生物调节和多细胞生物过程是最丰富的。KEGG 分析表明，TNF、P53 和 PI3K 信号网络可能是最有潜力的 ZWINT 相关途径，并通过 Western blot 分析得到验证。
ZWINT 可能是肺癌治疗的新靶点。
