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

Abstract
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.
AuthorsQu 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
JournalGenomics (Genomics) Vol. 114 Issue 2 Pg. 110265 (03 2022) ISSN: 1089-8646 [Electronic] United States
PMID35032618 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References
  • DNA
  • ALKBH1 protein, human
  • AlkB Homolog 1, Histone H2a Dioxygenase
  • N6AMT1 protein, human
  • Site-Specific DNA-Methyltransferase (Adenine-Specific)
Topics
  • AlkB Homolog 1, Histone H2a Dioxygenase (genetics)
  • Carcinoma, Hepatocellular (genetics, pathology)
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA (metabolism)
  • DNA Methylation
  • Gene Expression Regulation, Neoplastic
  • Genome
  • Humans
  • Liver Neoplasms (genetics, pathology)
  • Site-Specific DNA-Methyltransferase (Adenine-Specific) (genetics, metabolism)

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