Related Experiment Video
Updated: Dec 2, 2025

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
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.
Abstract:
Disruption of signaling pathways that plays a role in the normal development and cellular homeostasis may lead to the dysregulation of cellular signaling and bring about the onset of different diseases, including cancer. In addition to genetic aberrations, DNA methylation also acts as an epigenetic modifier to drive the onset and progression of cancer by mediating the reversible transcription of related genes. Although the role of DNA methylation as an alternative driver of carcinogenesis has been well-established, the global effects of DNA methylation on oncogenic signaling pathways and the presentation of cancer is only emerging. In this article, we introduced a differential methylation parsing pipeline (MethylMine) which mined for epigenetic biomarkers based on feature selection. This pipeline was used to mine for biomarkers, which presented a substantial difference in methylation between the tumor and the matching normal tissue samples. Combined with the Data Integration Analysis for Biomarker discovery (DIABLO) framework for machine learning and multi-omic analysis, we revisited the TCGA DNA methylation and RNA-Seq datasets for breast, colorectal, lung, and prostate cancer, and identified differentially methylated genes within the NRF2-KEAP1/PI3K oncogenic pathway, which regulates the expression of cytoprotective genes, that serve as potential therapeutic targets to treat different cancers.
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.
Related Concept Videos
Epigenetic Regulation
X-chromosome...
Epigenetic Regulation
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
Abnormal Proliferation

