A profile of 8-oxo-dGTPase activities in the NCI-60 human cancer panel: Meta-analytic insight into the regulation and role of MTH1 (NUDT1) gene expression in carcinogenesis

• Published in: Free radical biology & medicine Vol. 148; pp. 1 - 21
• Main Authors: Bialkowski, Karol, Kasprzak, Kazimierz S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.02.2020
• Subjects: Carcinogenesis; Cell Line, Tumor; DNA Repair Enzymes - genetics; Gene Expression; Humans; Phosphoric Monoester Hydrolases - genetics
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2019.12.036

We measured the specific 8-oxo-dGTPase activity profile of the NCI-60 panel of malignant cell lines, and MTH1 protein levels in a subset of 16 lines. Their 8-oxo-dGTPase activity was compared to twelve publicly accessible MTH1 mRNA expression data bases and their cross-consistency was analyzed. 8-oxo-dGTPase and MTH1 protein levels in these cell lines are generally, but not always, mainly determined by MTH1 mRNA expression levels. The aneuploidy number of MTH1 gene copies only slightly affects its mRNA expression levels. By using the data mining platforms Compare and CellMiner, our 8-oxo-dGTPase profile was compared to five global gene expression datasets to identify genes whose expression levels are directly or inversely associated with 8-oxo-dGTPase. We analyzed effects of SNP within MTH1 on MTH1 mRNA level and enzyme activity. Similar association analysis was performed for five microRNA expression datasets. We identified several proteins and microRNA which might be involved in the regulation of MTH1 expression and we discuss potential mechanisms. Comparison of chemical and natural products sensitivities of the NCI-60 panel suggests seven compounds which are directly or inversely associated with 8-oxo-dGTPase. We provide an integrated picture of MTH1 expression combined from eleven consistent MTH1 mRNA and our 8-oxo-dGTPase activity NCI-60 profiles. [Display omitted] •A profile of 8-oxo-dGTPase activity of MTH1 protein in NCI-60 cell lines.•8-oxo-dGTPase activity is predetermined by mRNA level in cancer cells.•Associations of 8-oxo-dGTPase with cellular molecular targets and sensitivity to chemicals.