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DNA N6-methyladenine involvement and regulation of hepatocellular carcinoma development.

Authors:
Qu Lin Jun-Wei Chen Hao Yin Ming-An Li Chu-Ren Zhou Tao-Fang Hao Tao Pan Chun Wu Zheng-Ran Li Duo Zhu Hao-Fan Wang Ming-Sheng Huang

Genomics 2022 03 13;114(2):110265. Epub 2022 Jan 13.

Department of Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Department of Interventional Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China. Electronic address:

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.

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http://dx.doi.org/10.1016/j.ygeno.2022.01.002DOI Listing
March 2022

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