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An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
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Integrative Analysis Reveals Comprehensive Altered Metabolic Genes Linking with Tumor Epigenetics Modification in

Yahui Shi1, Jinfen Wei1, Zixi Chen1

  • 1School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.

Biomed Research International
|December 13, 2019
PubMed
Abstract

Insights

This study reveals key metabolic genes linked to epigenetic changes in cancer. Deregulation of these genes, like DNMT3B, impacts cancer progression and suggests new therapeutic targets.

Area of Science:

  • Oncology
  • Epigenetics
  • Cancer Metabolism

Background:

  • Cancer cells exhibit metabolic reprogramming and epigenetic dysfunction to meet biosynthetic demands.
  • While metabolic reprogramming is studied, the link between global metabolic genes and epigenetics in pan-cancer remains underexplored.

Purpose of the Study:

  • To identify critical metabolic signatures with differential expression contributing to epigenetic alterations across various cancer types.
  • To uncover potential therapeutic targets for cancer treatment by understanding these metabolic and epigenetic links.

Main Methods:

  • Analysis of differential gene expression and DNA methylation using 5726 samples from The Cancer Genome Atlas (TCGA).
  • Comparison with Gene Expression Omnibus (GEO) database data to validate metabolic gene expression trends.
  • Construction of regulatory networks for histone acetylation and DNA methylation based on altered metabolic gene expression.

Main Results:

  • Confirmed overall metabolism reprogramming in cancer with consistent expression trends across datasets.
  • Identified a regulatory network linking metabolic gene expression to histone acetylation and DNA methylation.
  • High expression of DNA methyltransferase 3B (DNMT3B) correlated with poorer overall survival in 5 cancer types.
  • DNMT3B influences tissue-specific DNA methylation, affecting distinct gene sets across different cancers.

Conclusions:

  • Key metabolic genes (ACLY, SLC2A1, KAT2A, DNMT3B) are significantly disordered, contributing to epigenetic dysfunction in cancer.
  • DNMT3B plays a role in tissue-specific epigenetic alterations in cancer.
  • The study highlights epigenetic disorders arising from metabolic gene deregulation in pan-cancer, offering potential therapeutic strategies.

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