Related Experiment Video
Updated: Oct 1, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Identification of the upstream regulators of KDM5B in gastric cancer
Long-Fei Zhao1, Feng-Yu Qi1, Jin-Ge Zhang1
1Key Lab of Advanced Drug Preparation Technologies, Ministry of Education of China, State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Henan Province for Drug Quality and Evaluation, Institute of Drug Discovery and Development, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.
Aims:
Lysine-specific demethylase 5B (KDM5B) is an epigenetic regulator of chromatin that catalyzes the demethylation of histone 3 lysine 4. It is overexpressed in multiple cancer types and acts as a therapeutic target in cancer therapy. Nevertheless, its upstream regulatory pathway is not completely understood, prompting the search for the underlying biological factors driving KDM5B overexpression.
Materials And Methods:
A comprehensive analysis was performed to examine the association between KDM5B overexpression and copy number variation (CNV), somatic mutation, mRNA expression, miRNA expression, and clinical characters from The Cancer Genome Atlas database. Coexpression and function enrichment analyses were performed with KDM5B-coexpressed genes. The gastric cancer (GC) cell line MKN45 was utilized to verify the regulation of KDM5B using the transcription factor (TF) Yin Yang 1 (YY1) and miR-29a-3p.
Key Findings:
KDM5B was overexpressed and associated with poor prognosis in GC. KDM5B upregulation was driven by CNV amplification and DNA hypomethylation rather than by KDM5B mutations. Enrichment analysis revealed that KDM5B-coexpressed genes were primarily related to the transmembrane transport function and the ubiquitin-mediated proteolysis signaling pathway. As a TF, YY1 might bind to the KDM5B promoter region to regulate KDM5B expression. In addition, miR-29a-3p might bind to and negatively regulate KDM5B expression.
Significance:
Our results demonstrate that KDM5B expression is regulated via CNV amplification, DNA hypomethylation, and YY1 and miR-29a-3p; KDM5B expression regulation is associated with patient survival and tumor cell proliferation.
Insights
Lysine-specific demethylase 5B (KDM5B) is overexpressed in gastric cancer due to copy number amplification and DNA hypomethylation. Its regulation involves transcription factor YY1 and miR-29a-3p, impacting patient survival.
Area of Science:
- Epigenetics
- Cancer Biology
- Molecular Oncology
Background:
- Lysine-specific demethylase 5B (KDM5B) is an epigenetic regulator overexpressed in various cancers, presenting a therapeutic target.
- Understanding the upstream regulatory pathways driving KDM5B overexpression is crucial for effective cancer therapy.
Purpose of the Study:
- To investigate the regulatory mechanisms underlying KDM5B overexpression in cancer.
- To identify biological factors and pathways associated with KDM5B dysregulation.
Main Methods:
- Comprehensive analysis of The Cancer Genome Atlas (TCGA) data, including copy number variation (CNV), mutations, and mRNA/miRNA expression.
- Coexpression and functional enrichment analyses of KDM5B-associated genes.
- Experimental validation in gastric cancer (GC) cell lines using transcription factor (TF) Yin Yang 1 (YY1) and miR-29a-3p.
Main Results:
- KDM5B overexpression correlates with poor prognosis in gastric cancer.
- KDM5B upregulation is primarily driven by CNV amplification and DNA hypomethylation, not somatic mutations.
- Coexpressed genes are enriched in transmembrane transport and ubiquitin-mediated proteolysis pathways.
- YY1 may promote KDM5B expression, while miR-29a-3p may inhibit it.
Conclusions:
- KDM5B expression is regulated by genetic (CNV amplification) and epigenetic (DNA hypomethylation) alterations, as well as transcriptional (YY1) and post-transcriptional (miR-29a-3p) mechanisms.
- KDM5B regulation impacts gastric cancer patient survival and tumor cell proliferation.
More Related Videos
Related Concept Videos
02:23Master Transcription Regulators
02:23Abnormal Proliferation
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...