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- W3020545168 endingPage "1031" @default.
- W3020545168 startingPage "1031" @default.
- W3020545168 abstract "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." @default.
- W3020545168 created "2020-05-01" @default.
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- W3020545168 date "2020-04-21" @default.
- W3020545168 modified "2023-10-12" @default.
- W3020545168 title "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" @default.
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- W3020545168 doi "https://doi.org/10.3390/cells9041031" @default.
- W3020545168 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7226174" @default.
- W3020545168 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32326378" @default.
- W3020545168 hasPublicationYear "2020" @default.