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Sci Rep. 2019 Jan 29;9(1):868. doi: 10.1038/s41598-018-37340-w.

Comprehensive profiling of JMJD3 in gastric cancer and its influence on patient survival.

Xu Z1, Xia Y2, Xiao Z3,4, Jia Y5, Li L6, Jin Y2, Zhao Q3,4, Wan L7, Yi T8, Yu Y9, Wen Q10, Zhu Y11, Qin B12,13, Zhang F14, Shen J15,16.

Author information

1
Precision Medicine centre, Yijishan Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, PR China.
2
Department of Gastrointestinal Surgery, Yijishan Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, PR China.
3
Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China.
4
South Sichuan Institution for Translational Medicine, Luzhou, 646000, Sichuan, PR China.
5
Department of Gastroenterology, Yijishan Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, China.
6
Department of Gynecology and Obstetrics, Yijishan Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, China.
7
Department of Hematology and Oncology, The Children's Hospital of Soochow, Jiangsu, China.
8
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
9
Center for Diabetes, Obesity and Metabolism, Department of Physiology, Shenzhen University Health Science Center, Shenzhen, Guangdong province, PR China.
10
Department of Oncology, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, 646000, P.R. China.
11
Department of Gastroenterology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, PR China.
12
Shenzhen Key Laboratory of Ophthalmology, Shenzhen University, Shenzhen, 518040, Guangdong, China. qinbozf@163.com.
13
Department of Ophthalmology, Shenzhen Shekou People's Hospital, Shenzhen, Guangdong Province, P. R. China. qinbozf@163.com.
14
Department of Pathology, Yijishan Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, China. zhangfan401401@aliyun.com.
15
Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China. crystal_stray@126.com.
16
South Sichuan Institution for Translational Medicine, Luzhou, 646000, Sichuan, PR China. crystal_stray@126.com.

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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