Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, No. 1 Beiguandajie, Tongzhou District, Beijing, 101149, China.
Department of Cellular and Molecular Biology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China.
BMC Med Genomics. 2020 Nov 4;13(1):166. doi: 10.1186/s12920-020-00816-8.
Hypoxia and stemness are important factors in tumor progression. We aimed to explore the ncRNA classifier associated with hypoxia and stemness in lung adenocarcinoma (LUAD). We found that the prognosis of LUAD patients with high hypoxia and stemness index was worse than that of patients with low hypoxia and stemness index. RNA expression profiles of these two clusters were analyzed, and 6867 differentially expressed (DE) mRNAs were screened. Functional analysis showed that DE mRNAs were associated with cell cycle and DNA replication. Protein-protein interaction network analysis revealed 20 hub genes, among which CENPF, BUB1, BUB1B, KIF23 and TTK had significant influence on prognosis. In addition, 807 DE lncRNAs and 243 DE miRNAs were identified. CeRNA network analysis indicated that AC079160.1-miR-539-5p-CENPF may be an important regulatory axis that potentially regulates the progression of LUAD. The expression of AC079160.1 and CENPF were positively correlated with hypoxia and stemness index, while miR-539-5p expression level was negatively correlated with hypoxia and stemness index. Overall, we identified CENPF, BUB1, BUB1B, KIF23 and TTK as potentially key genes involved in regulating hypoxia-induced tumor cell stemness, and found that AC079160.1-miR-539-5p-CENPF axis may be involved in regulating hypoxia induced tumor cell stemness in LUAD.
缺氧和干性是肿瘤进展的重要因素。我们旨在探索与肺腺癌（LUAD）缺氧和干性相关的非编码 RNA 分类器。我们发现，具有高缺氧和干性指数的 LUAD 患者的预后比具有低缺氧和干性指数的患者差。分析了这两个聚类的 RNA 表达谱，筛选出 6867 个差异表达（DE）mRNA。功能分析表明，DE mRNAs 与细胞周期和 DNA 复制有关。蛋白质-蛋白质相互作用网络分析揭示了 20 个枢纽基因，其中 CENPF、BUB1、BUB1B、KIF23 和 TTK 对预后有显著影响。此外，还鉴定出 807 个 DE lncRNAs 和 243 个 DE miRNAs。CeRNA 网络分析表明，AC079160.1-miR-539-5p-CENPF 可能是一个重要的调控轴，可能调节 LUAD 的进展。AC079160.1 和 CENPF 的表达与缺氧和干性指数呈正相关，而 miR-539-5p 的表达水平与缺氧和干性指数呈负相关。总的来说，我们确定了 CENPF、BUB1、BUB1B、KIF23 和 TTK 作为潜在的关键基因，参与调节缺氧诱导的肿瘤细胞干性，并发现 AC079160.1-miR-539-5p-CENPF 轴可能参与调节 LUAD 中缺氧诱导的肿瘤细胞干性。
