Shin Ki-Hyuk, Kang Mo K, Park No-Hee
School of Dentistry, Dental Research Institute, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA.
Nitric Oxide. 2008 Sep;19(2):125-32. doi: 10.1016/j.niox.2008.04.012. Epub 2008 Apr 24.
Nitric oxide (NO) is a multifunctional regulator, critical to various biochemical processes, including inflammation, vasodilatation, intra- and intercellular signaling, apoptosis, and carcinogenesis. In particular, recent studies have indicated the association between elevated NO production and neoplastic cell transformation, suggesting procarcinogenic effects of NO. To investigate the mechanism by which NO facilitates oral carcinogenesis, we tested the effects of exogenous NO on the expression of hnRNP G, a novel protein demonstrating tumor suppressive effects against oral squamous cell carcinomas. Oral epithelial cells exposed to NO donor demonstrated significant reduction in the level of hnRNP G protein and mRNA expression. Also, exposure to NO donor led to decreased hnRNP G promoter activity in cells, indicating that NO negatively regulates hnRNP G expression at the level of transcription. Since hnRNP G expression is markedly decreased or completely abolished in precancerous and malignant oral lesions in situ, these results suggest the possibility that NO facilitates the progression of the disease by targeting hnRNP G expression. In this article, we review the role of hnRNP G in tumor suppression and maintenance of genetic integrity, with focus on its potential association with NO in the context of oral carcinogenesis.
一氧化氮（NO）是一种多功能调节剂，对包括炎症、血管舒张、细胞内和细胞间信号传导、细胞凋亡及致癌作用在内的各种生化过程至关重要。特别是，最近的研究表明，NO生成增加与肿瘤细胞转化之间存在关联，提示NO具有促癌作用。为了探究NO促进口腔癌发生的机制，我们测试了外源性NO对hnRNP G表达的影响，hnRNP G是一种对口腔鳞状细胞癌具有肿瘤抑制作用的新型蛋白质。暴露于NO供体的口腔上皮细胞显示hnRNP G蛋白水平和mRNA表达显著降低。此外，暴露于NO供体导致细胞中hnRNP G启动子活性降低，表明NO在转录水平上对hnRNP G表达起负调控作用。由于在癌前和恶性口腔原位病变中hnRNP G表达明显降低或完全缺失，这些结果提示这些结果提示NO可能通过靶向hnRNP G表达促进疾病进展。在本文中，我们综述了hnRNP G在肿瘤抑制和维持遗传完整性中的作用，重点关注其在口腔癌发生背景下与NO的潜在关联。
