Academic Journal

The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

التفاصيل البيبلوغرافية
العنوان: The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells
المؤلفون: Sotirios G. Doukas, Dimitra P. Vageli, George Lazopoulos, Demetrios A. Spandidos, Clarence T. Sasaki, Aristidis Tsatsakis
المصدر: Cells, Vol 9, Iss 4, p 1031 (2020)
بيانات النشر: MDPI AG, 2020.
سنة النشر: 2020
المجموعة: LCC:Cytology
مصطلحات موضوعية: tobacco smoke, NNK, head and neck cancer, lung cancer, Mismatch DNA repair, MSH2, Cytology, QH573-671
الوصف: Tobacco smoking is a common risk factor for lung cancer and head and neck cancer. Molecular changes such as deregulation of miRNA expression have been linked to tobacco smoking in both types of cancer. Dysfunction of the Mismatch DNA repair (MMR) mechanism has also been associated with a poor prognosis of these cancers, while a cross-talk between specific miRNAs and MMR genes has been previously proposed. We hypothesized that exposure of lung and head and neck squamous cancer cells (NCI and FaDu, respectively) to tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is capable of altering the expression of MSH2 and MLH1, key MMR components, by promoting specific miRNA deregulation. We found that either a low (1 μM) or high (2 μM) dose of NNK induced significant upregulation of “oncomirs” miR-21 and miR-155 and downregulation of “tumor suppressor” miR-422a, as well as the reduction of MMR protein and mRNA expression, in NCI and FaDu, compared to controls. Inhibition of miR-21 restored the NNK-induced reduced MSH2 phenotype in both NCI and FaDu, indicating that miR-21 might contribute to MSH2 regulation. Finally, NNK exposure increased NCI and FaDu survival, promoting cancer cell progression. We provide novel findings that deregulated miR-21, miR-155, and miR-422a and MMR gene expression patterns may be valuable biomarkers for lung and head and neck squamous cell cancer progression in smokers.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2073-4409
Relation: https://www.mdpi.com/2073-4409/9/4/1031; https://doaj.org/toc/2073-4409
DOI: 10.3390/cells9041031
URL الوصول: https://doaj.org/article/4c0d48666f38467590705e97d8b3e1ef
رقم الانضمام: edsdoj.4c0d48666f38467590705e97d8b3e1ef
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20734409
DOI:10.3390/cells9041031