Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Cell-based Drug and Health Product Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Cancer Genomics Proteomics. 2020 Jul-Aug;17(4):401-415. doi: 10.21873/cgp.20199.
BACKGROUND/AIM: Nitric oxide (NO) is recognized as an important biological mediator that exerts several human physiological functions. As its nature is an aqueous soluble gas that can diffuse through cells and tissues, NO can affect cell signaling, the phenotype of cancer and modify surrounding cells. The variety of effects of NO on cancer cell biology has convinced researchers to determine the defined mechanisms of these effects and how to control this mediator for a better understanding as well as for therapeutic gain.
We used bioinformatics and pharmacological experiments to elucidate the potential regulation and underlying mechanisms of NO in non-small a lung cancer cell model.
Using microarrays, we identified a total of 151 NO-regulated genes (80 up-regulated genes, 71 down-regulated genes) with a strong statistically significant difference compared to untreated controls. Among these, the genes activated by a factor of more than five times were: DCBLD2, MGC24975, RAB40AL, PER3, RCN1, MRPL51, PTTG1, KLF5, NFIX. On the other hand, the expression of RBMS2, PDP2, RBAK, ORMDL2, GRPEL2, ZNF514, MTHFD2, POLR2D, RCBTB1, JOSD1, RPS27, GPR4 genes were significantly decreased by a factor of more than five times. Bioinformatics further revealed that NO exposure of lung cancer cells resulted in a change in transcription factors (TFs) and epigenetic modifications (histone modification and miRNA). Interestingly, NO treatment was shown to potentiate cancer stem cell-related genes and transcription factors Oct4, Klf4, and Myc.
Through this comprehensive approach, the present study illustrated the scheme of how NO affects molecular events in lung cancer cells.
背景/目的：一氧化氮（NO）是一种重要的生物介质，具有多种人体生理功能。由于其性质为水溶性气体，可扩散通过细胞和组织，NO 可以影响细胞信号转导、癌症表型并修饰周围细胞。NO 对癌细胞生物学的多种影响使研究人员确信要确定这些影响的明确机制，以及如何控制这种介质，以更好地理解和获得治疗效果。
我们使用生物信息学和药理学实验来阐明 NO 在非小细胞肺癌细胞模型中的潜在调节和潜在机制。
使用微阵列，我们总共鉴定了 151 个 NO 调节基因（80 个上调基因，71 个下调基因），与未处理的对照组相比，具有很强的统计学显着差异。在这些基因中，激活因子超过五倍的基因有：DCBLD2、MGC24975、RAB40AL、PER3、RCN1、MRPL51、PTTG1、KLF5、NFIX。另一方面，RBMS2、PDP2、RBAK、ORMDL2、GRPEL2、ZNF514、MTHFD2、POLR2D、RCBTB1、JOSD1、RPS27、GPR4 基因的表达显著下降了五倍以上。生物信息学进一步表明，NO 暴露于肺癌细胞会导致转录因子（TFs）和表观遗传修饰（组蛋白修饰和 miRNA）发生变化。有趣的是，NO 处理被证明可增强与癌症干细胞相关的基因和转录因子 Oct4、Klf4 和 Myc。
通过这种综合方法，本研究说明了 NO 如何影响肺癌细胞中分子事件的方案。
