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

P1.05. Research on Specific DNA Methylation Regulatory Mechanism Based on Pan-Cancer Analysis - PDF(Slides)

Pdf Summary

This research study, conducted by Dr. Yvan Guo, Dr. Jie Gu, and Dr. Di Ge at Zhongshan Hospital in Shanghai, China, focuses on understanding the regulation of DNA methylation and its implications in cancer. The study aims to address the limitations of current demethylation therapy, which is hindered by unspecific hypomethylation of oncogenes.<br /><br />Using pan-cancer datasets, the researchers developed a deep learning framework, called mrBox, to identify 11 classes of DNA methylation regulatory sequences. These sequences were found to have distinct effects on clinical outcomes based on the methylation levels of CpG sites. To validate their findings, the researchers used CRISPR/Cas9 to knock out the regulatory sequences and developed an intracellular CpG methylation reporter system.<br /><br />Further analysis revealed that methylation regulatory sequences interacted with nuclear proteins, including DNMT1 and U1 spliceosome markers. The researchers also discovered a specific methylation regulatory mechanism involving U1 snRNP and noncoding RNAs that regulates the chromatin retention of DNMT1.<br /><br />Overall, this study provides valuable insights into the specific mechanisms of DNA methylation regulation and its potential implications for epigenetic therapy in cancer. The findings suggest that targeting specific methylation regulatory sequences could improve the effectiveness of demethylation therapy.

Asset Subtitle

Yvan Guo

Meta Tag

Speaker Yvan Guo

Topic Tumor Biology: Preclinical Biology - Regulatory Mechanisms

Keywords

DNA methylation

cancer

regulation

demethylation therapy

oncogenes

mrBox

deep learning framework

CpG sites

CRISPR/Cas9

methylation regulatory sequences