AI Article Synopsis
- Histone methylation influences gene regulation, with abnormalities linked to cancer; JMJD3 is a demethylase that plays a context-specific role in tumor development.
- This study investigates JMJD3's expression in gastric cancer, revealing that high levels correlate with poor patient survival and serve as an independent prognostic indicator.
- Findings suggest that genetic mutations and DNA methylation contribute to JMJD3 deregulation, highlighting its potential as a therapeutic target, with inhibitors like GSK-J4 showing promise in countering its oncogenic effects.
Article Abstract
Histone methylation is thought to control the regulation of genetic program and the dysregulation of it has been found to be closely associated with cancer. JMJD3 has been identified as an H3K27 demethylase and its role in cancer development is context specific. The role of JMJD3 in gastric cancer (GC) has not been examined. In this study, JMJD3 expression was determined. The prognostic significance of JMJD3 and its association with clinical parameters were evaluated. JMJD3 dysregulation mechanism and targets were analyzed. The effect of JMJD3 mutation was determined by functional study. Results showed that JMJD3 was overexpressed in different patient cohorts and also by bioinformatics analysis. High JMJD3 expression was correlated with shortened overall survival in patients with GC and was an independent prognosis predictor. Genetic aberration and DNA methylation might be involved in the deregulation of JMJD3 in GC. Downstream network of JMJD3 was analyzed and several novel potential targets were identified. Furthermore, functional study discovered that both demethylase-dependent and demethylase-independent mechanisms were involved in the oncogenic role of JMJD3 in GC. Importantly, histone demethylase inhibitor GSK-J4 could reverse the oncogenic effect of JMJD3 overexpression. In conclusion, our study report the oncogenic role of JMJD3 in GC for the first time. JMJD3 might serve as an important epigenetic therapeutic target and/or prognostic predictor in GC.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351656 | PMC |
| http://dx.doi.org/10.1038/s41598-018-37340-w | DOI Listing |
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