Glucosamine‐phosphate N‐acetyltransferase 1 and its DNA methylation can be biomarkers for the diagnosis and prognosis of lung cancer

• Published in: Journal of clinical laboratory analysis 2022-09, Vol.36 (9), p.e24628-n/a
• Main Authors: Ding, Peikun, Peng, Bin, Li, Guofeng, Sun, Xuefeng, Wang, Guangsuo
• Format: Article
• Language: English
• Subjects: Acetyltransferase; Biomarker; Biomarkers; Cell migration; Cell viability; Cholecystokinin; Cyclin D1; Diagnosis; DNA methylation; Genes; Genomes; Genomics; Glucosamine; GNPNAT1; Immunohistochemistry; Lung cancer; Matrix metalloproteinase; Medical prognosis; Medical research; Metalloproteinase; mRNA; Plasmids; Principal components analysis; Prognosis; Tissue inhibitor of metalloproteinases; Trends; Vimentin; Xenografts
• ISSN: 0887-8013; 1098-2825
• DOI: 10.1002/jcla.24628

Objective Lung cancer ranking high in the cancer‐related list has long perplexed patients, in which glucosamine‐phosphate N‐acetyltransferase 1 (GNPNAT1) is found to be highly expressed. Besides, DNA methylation is perceived as a biomarker to assess the prognosis of patients with various cancers. However, the correlation between GNPNAT1 and DNA methylation and the role of GNPNAT1 in lung cancer remain vague. Methods Principal component analysis (PCA), heatmap, volcano map, Venn diagram, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to screen out the candidate genes. The viability, migration, and invasion of lung cancer cells were detected by CCK‐8 and Transwell assays. An xenograft tumor mouse model was established. The relative expressions of GNPNAT1, E‐cadherin, vimentin, Matrix metalloproteinase‐2 (MMP‐2), tissue inhibitor of metalloproteinase‐2 (TIMP‐2), E2F1, and cyclin D1 in cells or xenograft tumor tissues were quantified by Western blot, RT‐qPCR, or immunohistochemistry assay. Results GNPNAT1 was screened as the research object. GNPNAT1 methylation was downregulated, while GNPNAT1 expression was upregulated in lung cancer tissues. The methylation and mRNA levels of GNPNAT1 were correlated with the patient prognosis. GNPNAT1 increased cell viability, migration and invasion, and promoted the xenograft tumor volume and weight, whereas shGNPNAT1 acted oppositely. Moreover, expressions of Vimentin, MMP‐2, E2F1, and cyclin D1 were increased, but E‐cadherin and TIMP‐2 expressions were decreased by overexpressed GNPNAT1, whilst GNPNAT1 knockdown ran conversely. Conclusion GNPNAT1 and methylated GNPNAT1 coverage are biomarkers for the diagnosis and prognosis of lung cancer. Lung cancer ranked high in the cancer‐related list perplexes patients and glucosamine‐phosphate N‐acetyltransferase 1 (GNPNAT1) is found upregulated in lung cancer. DNA methylation is perceived as a biomarker to assess prognosis for cancers. However, the correlation between GNPNAT1 and DNA methylation and the role of GNPNAT1 in lung cancer remain vague. In this study, we discovered that GNPNAT1 methylation was downregulated, while GNPNAT1 expression was upregulated in cancer tissues. GNPNAT1 increased cell viability, migration and invasion, and promoted the xenograft tumor volume and weight, while shGNPNAT1 acted oppositely. Our study revealed that GNPNAT1 and methylated GNPNAT1 coverage be biomarkers for the diagnosis and prognosis of lung can