Regulation of Canonical Oncogenic Signaling Pathways in Cancer via DNA Methylation

Jennifer Lu1,2, Premila Wilfred1,2, Darren Korbie1,2

  • 1Centre for Personalised Nanomedicine, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia.

Cancers
|November 4, 2020
PubMed

Insights

This study introduces MethylMine, a new pipeline for identifying epigenetic biomarkers. It found key DNA methylation differences in cancer pathways, offering potential new therapeutic targets.

Area of Science:

  • Oncology
  • Epigenetics
  • Bioinformatics

Background:

  • Cellular signaling pathway disruption contributes to cancer development.
  • DNA methylation is an epigenetic mechanism influencing gene transcription and cancer progression.
  • The global impact of DNA methylation on oncogenic pathways is an emerging area of research.

Purpose of the Study:

  • To introduce MethylMine, a novel pipeline for identifying epigenetic biomarkers.
  • To investigate the role of DNA methylation in oncogenic signaling pathways across multiple cancer types.
  • To identify potential therapeutic targets based on differential DNA methylation.

Main Methods:

  • Developed and utilized the MethylMine pipeline for feature selection and biomarker discovery.
  • Employed the Data Integration Analysis for Biomarker discovery (DIABLO) framework for machine learning and multi-omic analysis.
  • Analyzed TCGA DNA methylation and RNA-Seq datasets for breast, colorectal, lung, and prostate cancers.

Main Results:

  • Identified differentially methylated genes using the MethylMine pipeline.
  • Discovered significant methylation differences in the NRF2-KEAP1/PI3K pathway.
  • Highlighted specific genes within this pathway as potential therapeutic targets.

Conclusions:

  • MethylMine is effective in identifying epigenetic biomarkers associated with cancer.
  • Differential DNA methylation within the NRF2-KEAP1/PI3K pathway is implicated in various cancers.
  • The identified differentially methylated genes represent promising targets for cancer therapy.

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