Huang Hongbo, Hua Qingwang
Department of Thoracic Surgery, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China.
Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China.
Int J Genomics. 2022 Apr 30;2022:8348499. doi: 10.1155/2022/8348499. eCollection 2022.
Nei endonuclease VIII-like 3 (NEIL3) is widely involved in pathophysiological processes of the body; however, its role in lung cancer has not been conclusively determined.
This study is aimed at exploring the role of NEIL3 in lung cancer.
The public data used in this study were downloaded from The Cancer Genome Atlas (TCGA) database. "Limma" in R was used for the analysis of differentially expressed genes. Clinical correlations and prognostic analyses were performed using the survival package in R. The proliferative abilities of lung cancer cells were evaluated by the CCK8 and colony formation assays while their invasive and migration abilities were assessed by the transwell and wound healing assays. Quantitative real-time PCR (qRT-PCR) and western blot analyses were utilized to detect RNA and protein levels. Biological differences between groups were determined by gene set enrichment analysis (GSEA). Tumor Immune Dysfunction and Exclusion (TIDE) as well as Genomics of Drug Sensitivity in Cancer (GDSC) was used for immunotherapeutic and chemotherapeutic sensitivity analyses.
NEIL3 was upregulated in NSCLC tissues and cell lines, implying that it is involved in lung cancer initiation and progression. Clinical correlation and prognostic analyses showed that NEIL3 was associated with worse clinical features (stage and T and N classifications) and poor prognostic outcomes. , NEIL3 significantly enhanced NSCLC proliferation, invasion, and migration. GSEA indicated that NEIL3 might be involved in PI3K/AKT/mTOR, G2/M checkpoints, and E2F target pathways. Inhibition of NEIL3 suppressed cyclinD1 and p-AKT protein levels; however, it had no effects on AKT levels, indicating that NEIL3 can partially activate the PI3K/AKT/mTOR signaling pathway. The predicted result of TIDE indicated that immunotherapeutic nonresponders had elevated NEIL3 levels. Moreover, there was a positive correlation between NEIL3 levels and chemosensitivity to cisplatin and paclitaxel.
In general, NEIL3 mediates NSCLC progression and affects sensitivity to immunotherapy and chemotherapy; therefore, it is a potential molecular target for treatment.
内核酸酶VIII样3（NEIL3）广泛参与机体的病理生理过程；然而，其在肺癌中的作用尚未最终确定。
本研究旨在探讨NEIL3在肺癌中的作用。
本研究使用的公共数据从癌症基因组图谱（TCGA）数据库下载。R语言中的“Limma”用于分析差异表达基因。使用R语言中的生存包进行临床相关性和预后分析。通过CCK8和集落形成试验评估肺癌细胞的增殖能力，同时通过Transwell和伤口愈合试验评估其侵袭和迁移能力。利用定量实时PCR（qRT-PCR）和蛋白质印迹分析检测RNA和蛋白质水平。通过基因集富集分析（GSEA）确定组间生物学差异。使用肿瘤免疫功能障碍与排除（TIDE）以及癌症药物敏感性基因组学（GDSC）进行免疫治疗和化疗敏感性分析。
NEIL3在非小细胞肺癌（NSCLC）组织和细胞系中上调，这意味着它参与肺癌的发生和发展。临床相关性和预后分析表明，NEIL3与较差的临床特征（分期以及T和N分类）和不良预后结果相关。此外，NEIL3显著增强NSCLC的增殖、侵袭和迁移。GSEA表明，NEIL3可能参与PI3K/AKT/mTOR、G2/M检查点和E2F靶标途径。抑制NEIL3可降低细胞周期蛋白D1和p-AKT蛋白水平；然而，它对AKT水平没有影响，这表明NEIL3可部分激活PI3K/AKT/mTOR信号通路。TIDE的预测结果表明，免疫治疗无反应者的NEIL3水平升高。此外，NEIL3水平与对顺铂和紫杉醇的化疗敏感性呈正相关。
总体而言，NEIL3介导NSCLC进展并影响免疫治疗和化疗敏感性；因此，它是一个潜在的治疗分子靶点。
