2023 World Conference on Lung Cancer (Posters)-P1.05. Research on Specific DNA Methylation Regulatory Mechanism Based on Pan-Cancer Analysis

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This presentation at the WCLC 2023 conference focused on researching the specific regulatory mechanisms of DNA methylation based on pan-cancer analysis. The authors mentioned that the outcome of recent demethylation therapy is limited due to the unspecific hypomethylation of oncogenes. They aimed to understand the distribution of DNA methylation in the same topological domain and its regulatory role.<br /><br />To achieve this, the authors established a framework to characterize and classify methylation regulatory DNA sequences using the TCGA pan-cancer datasets. They validated the identified sequences by knocking out the sequences surrounding the STING1 locus and confirming the hypomethylation of CpG sites related to STING1 expression. They also developed new methods to validate DNA sequences and characterize the molecular mechanism of DNA methylation regulation.<br /><br />The authors identified 11 classes of DNA methylation regulatory sequences with different compositions of repetitive sequences, covering a large number of CpG sites globally. Genes related to these different clusters of DNA methylation regulatory sequences were found to dominate different biological pathways. Knocking out regulatory sequences near the STING1 locus resulted in reduced DNA methylation and increased STING1 expression. <br /><br />Further analysis showed the enrichment of nuclear proteins and spliceosome-related proteins in the regulatory sequence group. The study also predicted long non-coding RNAs (lncRNAs) that could bind to methylation regulatory sequences and correlated the expression levels of these lncRNAs with CpG methylation levels. <br /><br />Overall, the authors discovered a specific methylation regulatory mechanism involving U1 snRNP and noncoding RNAs that regulate the chromatin retention of DNMT1. The authors believe that understanding this specific DNA methylation regulatory mechanism will contribute to the development of epigenetics therapy.<br /><br />Keywords: DNA methylation, Pan-cancer analysis<br />Session: Tumor Biology - Preclinical Biology - Regulatory Mechanisms<br />Presentation Number: P1.05-01<br />Track: 02. Tumor Biology - Preclinical Biology

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Yvan Guo

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Speaker Yvan Guo

Topic Tumor Biology: Preclinical Biology - Regulatory Mechanisms

Keywords

DNA methylation

regulatory mechanisms

pan-cancer analysis

demethylation therapy

TCGA datasets

STING1 locus

CpG sites

molecular mechanism

long non-coding RNAs

epigenetics therapy