COL1A1, PRPF40A, and UCP2 correlate with hypoxia markers in non-small cell lung cancer.
COL1A1, PRPF40A, and UCP2 correlate with hypoxia markers in non-small cell lung cancer.
复制标题
DOI：
10.1007/s00432-017-2381-y
复制
发表时间：
2017-07
影响因子：
3.6
通讯作者：
Xinarianos G
中科院分区：
文献类型：
--
作者：
Oleksiewicz U;Liloglou T;Tasopoulou KM;Daskoulidou N;Gosney JR;Field JK;Xinarianos G
胶原1A1 （COL1A1）、rna结合和mrna前体加工因子（PRPF40A）和解偶联蛋白2 （UCP2）被鉴定为细胞红蛋白（CYGB）的下游效应物，CYGB被证明与肿瘤生物学有关。虽然这三种基因以前与癌症有关，但对它们在肺部恶性肿瘤中的地位知之甚少。因此，我们研究了COL1A1、PRPF40A和UCP2在156例非小细胞肺癌（NSCLC）及其邻近正常组织中的表达和启动子甲基化。我们发现COL1A1和PRPF40A mrna在NSCLC中显著过表达（p < 1 × 10−4），而UCP2则有上调的趋势（p = 0.066）。只有COL1A1启动子在非小细胞肺癌中显示高甲基化（36%），这在鳞状细胞癌（p = 0.024）和中度至良好分化的肿瘤中尤为明显（p = 0.01）。COL1A1、PRPF40A和UCP2的转录水平与缺氧标志物的表达显著相关（p≤0.001）。此外，我们证明在缺氧或氧化应激的肺癌细胞系中，COL1A1转录对缺氧有显著的反应，而其他基因在应激条件下表现出适度的上调。总之，我们的数据显示COL1A1、UCP2和PRPF40A是参与NSCLC缺氧反应复杂网络的新参与者。
Collagen 1A1 (COL1A1), RNA-binding and pre-mRNA Processing Factor (PRPF40A), and Uncoupling Protein 2 (UCP2) were identified as downstream effectors of cytoglobin (CYGB), which was shown implicated in tumour biology. Although these three genes have been previously associated with cancer, little is known about their status in lung malignancies. Hereby, we investigated the expression and promoter methylation of COL1A1, PRPF40A, and UCP2 in 156 non-small cell lung cancer (NSCLC) and adjacent normal tissues. We demonstrate that COL1A1 and PRPF40A mRNAs are significantly overexpressed in NSCLC (p < 1 × 10−4), while UCP2 exhibits a trend of upregulation (p = 0.066). Only COL1A1 promoter revealed hypermethylation in NSCLCs (36%), which was particularly evident in squamous cell carcinomas (p = 0.024) and in the tumours with moderate-to-good differentiation (p = 0.01). Transcript level of COL1A1, as well as PRPF40A and UCP2, exhibited striking association (p ≤ 0.001) with the expression of hypoxia markers. In addition, we demonstrate in lung cancer cell lines exposed to hypoxia or oxidative stress that COL1A1 transcription significantly responds to oxygen depletion, while other genes showed the modest upregulation in stress conditions. In conclusion, our data revealed that COL1A1, UCP2, and PRPF40A are novel players implicated in the complex network of hypoxia response in NSCLC.