DNA N6-methyladenine involvement and regulation of hepatocellular carcinoma development

• Published in: Genomics (San Diego, Calif.) Calif.), 2022-03, Vol.114 (2), p.110265-110265, Article 110265
• Main Authors: Lin, Qu, Chen, Jun-wei, Yin, Hao, Li, Ming-an, Zhou, Chu-ren, Hao, Tao-fang, Pan, Tao, Wu, Chun, Li, Zheng-ran, Zhu, Duo, Wang, Hao-fan, Huang, Ming-sheng
• Format: Article
• Language: English
• Subjects: AlkB Homolog 1, Histone H2a Dioxygenase - genetics; ALKBH1; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Proliferation; DNA - metabolism; DNA Methylation; Gene Expression Regulation, Neoplastic; Genome; Genomic distribution; Hepatocellular carcinoma; Humans; Liver Neoplasms - genetics; Liver Neoplasms - pathology; N6-methyladenine; N6AMT1; Site-Specific DNA-Methyltransferase (Adenine-Specific) - genetics; Site-Specific DNA-Methyltransferase (Adenine-Specific) - metabolism
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2022.01.002

DNA N6-methyladenine (6 mA) is a new type of DNA methylation identified in various eukaryotic cells. However, its alteration and genomic distribution features in hepatocellular carcinoma (HCC) remain elusive. In this study, we found that N6AMT1 overexpression increased HCC cell viability, suppressed apoptosis, and enhanced migration and invasion, whereas ALKBH1 overexpression induced the opposite effects. Further, 23,779 gain-of-6 mA regions and 11,240 loss-of-6 mA regions were differentially identified in HCC tissues. The differential gain and loss of 6 mA regions were considerably enriched in intergenic regions. Moreover, 7% of the differential 6 mA modifications were associated with tumors, with 60 associated with oncogenes and 57 with tumor suppressor genes (TSGs), and 17 were common to oncogenes and TSGs. The candidate genes affected by 6 mA were filtered by gene ontology (GO) and RNA-seq. Using quantitative polymerase chain reaction (qPCR), BCL2 and PARTICL were found to be correlated with DNA 6 mA in certain HCC processes. •DNA 6 mA is significantly increased in HCC tissues with a specific genomic distribution.•N6AMT1 overexpression enhanced HCC cell viability, migration and invasion, suppressed apoptosis.•ALKBH1 overexpression suppressed HCC cell viability, migration and invasion, enhanced apoptosis.•BCL2 and PARTICL were shown to be correlated to DNA 6 mA in certain hepatic cancer processes.