Remodelin, a N-acetyltransferase 10 (NAT10) inhibitor, alters mitochondrial lipid metabolism in cancer cells.

Autor: Dalhat MH; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.; Centre for Artificial Intelligence in Precision Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.; Cancer and Mutagenesis Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Mohammed MRS; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.; Centre for Artificial Intelligence in Precision Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.; Cancer and Mutagenesis Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Ahmad A; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.; Centre for Artificial Intelligence in Precision Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.; Cancer and Mutagenesis Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Khan MI; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.; Centre for Artificial Intelligence in Precision Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.; Cancer and Mutagenesis Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Choudhry H; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.; Centre for Artificial Intelligence in Precision Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.; Cancer and Mutagenesis Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Jazyk: angličtina
Zdroj: Journal of cellular biochemistry [J Cell Biochem] 2021 Dec; Vol. 122 (12), pp. 1936-1945. Date of Electronic Publication: 2021 Oct 04.
DOI: 10.1002/jcb.30155
Abstrakt: Remodelin is a small molecule inhibitor of N-acetyltransferase 10 (NAT10), reported to reverse the effect of cancer conditions such as epithelial to mesenchymal transition, hypoxia, and drug resistance. We analysed RNA seq data of siNAT10 and found many metabolic pathways were altered, this made us perform unbiased metabolic analysis. Here we performed untargeted metabolomics in Remodelin treated cancer cells using high-performance liquid chromatography-tandem mass spectrometry. Statistical analysis revealed a total number of 138 of which 52 metabolites were significantly modified in Remodelin treated cells. Among the most significantly altered metabolites, we identified metabolites related with mitochondrial fatty acid elongation (MFAE) and mitochondrial beta-oxidation such as lauroyl-CoA, cholesterol, triglycerides, (S)-3-hydroxyhexadecanoyl-CoA, and NAD + . Furthermore, assessment showed alteration in expression of Enoyl-CoA hydratase, short chain 1, mitochondrial (ECHS1), and Mitochondrial trans-2-enoyl-CoA reductase (MECR) genes, associated with MFAE pathway. We also found statistically significant decrease in total cholesterol and triglycerides in Remodelin treated cancer cells. Overall, our results showed that Remodelin alters mitochondrial fatty acid metabolism and lipid accumulation in cancer cells. Finally, we validated these results in NAT10 knockdown cancer cells and found that NAT10 reduction results in alteration in gene expression associated with mitochondrial fatty acid metabolism, clearly suggesting the possible role of NAT10 in maintaining mitochondrial fatty acid metabolism.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
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