Heterogeneous nuclear ribonucleoprotein G, nitric oxide, and oral carcinogenesis.
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.
Shin
Ki-Hyuk
KH
School of Dentistry, Dental Research Institute, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA.
Kang
Mo K
MK
Park
No-Hee
NH
D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics*; D006801:Humans; D009062:Mouth Neoplasms / Q000209:etiology* / Q000473:pathology; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis
D034441:Heterogeneous-Nuclear Ribonucleoproteins; D020030:Nitric Oxide Donors; C510272:RBMX protein, human; D012333:RNA, Messenger; D009569:Nitric Oxide