Dept of Medical Oncology, ICMHO, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
Eur Respir J. 2013 May;41(5):1172-8. doi: 10.1183/09031936.00048712. Epub 2012 Jul 26.
The transcription factors SRY-related HMG box (SOX)2 and octamer-binding transcription factor (OCT)4 regulate the expression of the miR-302-367 cluster. miR-145 regulates SOX2 and OCT4 translation and p53 regulates miR-145 expression. We analysed the expression of the miR-302-367 cluster and miR-145 and the mutational status of p53 in resected nonsmall cell lung cancer (NSCLC) patients and correlated results with time to relapse (TTR). Tumour and paired normal tissue samples were obtained from 70 NSCLC patients. MicroRNA expression was assessed with TaqMan MicroRNA Assays. p53 exons 5 to 8 were sequenced. miR-145 was downregulated (p<0.0001) and miR-367 was upregulated (p<0.0001) in tumour compared with normal tissue. Mean TTR was 18.4 months for patients with low miR-145 levels and 28.2 months for those with high levels (p=0.015). Mean TTR was 29.1 months for patients with low miR-367 levels and 23.4 months for those with high levels (p=0.048). TTR was shorter for patients with both unfavourable variables (p=0.009). Low miR-145 expression (p=0.049), the combination of unfavourable microRNA levels (p=0.02) and the combination of low miR-145 with p53 mutations (p=0.011) were independent markers of shorter TTR. In conclusion, miR-145 and miR-367 expression could be novel markers for relapse in surgically treated NSCLC. p53 may play a role in modulating miR-145 expression in NSCLC.
转录因子 SRY 相关高迁移率族框 (SOX)2 和八聚体结合转录因子 (OCT)4 调节 miR-302-367 簇的表达。miR-145 调节 SOX2 和 OCT4 的翻译，p53 调节 miR-145 的表达。我们分析了 miR-302-367 簇和 miR-145 的表达以及 p53 的突变状态在切除的非小细胞肺癌 (NSCLC) 患者中的表达，并将结果与复发时间 (TTR) 相关联。从 70 名 NSCLC 患者中获得肿瘤和配对的正常组织样本。采用 TaqMan MicroRNA 分析评估 microRNA 表达。对 p53 外显子 5 到 8 进行测序。与正常组织相比，肿瘤组织中 miR-145 下调 (p<0.0001)，miR-367 上调 (p<0.0001)。miR-145 水平低的患者平均 TTR 为 18.4 个月，miR-145 水平高的患者为 28.2 个月 (p=0.015)。miR-367 水平低的患者平均 TTR 为 29.1 个月，miR-367 水平高的患者为 23.4 个月 (p=0.048)。两个不利变量均存在的患者 TTR 更短 (p=0.009)。miR-145 低表达 (p=0.049)、microRNA 水平不利组合 (p=0.02) 以及 miR-145 与 p53 突变的组合 (p=0.011) 是 TTR 较短的独立标志物。总之，miR-145 和 miR-367 的表达可能是手术治疗 NSCLC 复发的新标志物。p53 可能在调节 NSCLC 中 miR-145 的表达中起作用。
