Comprehensive profiling of JMJD3 in gastric cancer and its influence on patient survival
| Autor: | Yuliang Jia, Zhangang Xiao, Qinglian Wen, Lina Li, Fan Zhang, Qijie Zhao, Yabin Xia, Yan Jin, Yangyang Yu, Jing Shen, Bo Qin, Lin Wan, Zhenyu Xu, Yinxin Zhu, Tao Yi |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Jumonji Domain-Containing Histone Demethylases Bioinformatics analysis lcsh:Medicine Article Disease-Free Survival Histones 03 medical and health sciences 0302 clinical medicine Stomach Neoplasms Cell Line Tumor Histone methylation Humans Epigenetics lcsh:Science Aged Multidisciplinary biology lcsh:R Patient survival Benzazepines DNA Methylation Middle Aged Prognosis Pyrimidines 030104 developmental biology Histone Cell culture DNA methylation Cancer research biology.protein Demethylase lcsh:Q Female 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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