脱甲基酶
癌症研究
生物
组蛋白
异位表达
表观遗传学
组蛋白H3
基因表达
细胞生物学
分子生物学
化学
细胞培养
基因
生物化学
遗传学
作者
Zhangang Xiao,Jing Shen,Qijie Zhao,Shixin Xiang,Yinxin Zhu,Mingtao Xiao,Chi Han Li,Chi Hin Cho,Joanna H. Tong,Ka‐Fai To,Yangchao Chen
出处
期刊:Research Square - Research Square
日期:2020-05-22
被引量:1
标识
DOI:10.21203/rs.3.rs-30041/v1
摘要
Abstract Background : JMJD3 is a jmjd domain containing histone demethylase which can remove methyl groups from lysine 27 of histone 3 (H3K27) to active histone methylated genes. Previous studies have demonstrated that JMJD3 played a crucial role in inflammation. Methods : Our study showed that JMJD3 was significantly down-regulated in pancreatic ductal adenocarcinoma (PDAC) cell lines and tissues. Restored expression of JMJD3 inhibited oncogenic phenotypes of PDAC cells, including cell proliferation, cell migration, and in vivo tumorigenicity, indicating a tumor suppressive role. Gene-expression microarray revealed that Hexokinase domain containing 1 (HKDC1) was one of the JMJD3 downstream targets. Results : The expression of JMJD3 and HKDC1 in PDAC tissues was positively correlated. High H3K27 tri-methylation (H3K27me3) status in HKDC1 gene was attenuated by ectopic expression of JMJD3 in PDAC cells, suggested that JMJD3 regulated HKDC1 expression by histone demethylation activity. The tumor suppressive role of HKDC1 in PDAC was also proved. Moreover, HKDC1 was demonstrated to competitively bind to spectrin beta Ⅱ to induce cytoskeleton disruption, which may contribute to tumor suppression. Conclusion : Taken together, our study indicates that JMJD3 may disrupt spectrin-dependent cytoskeleton via activation of HKDC1 to suppress PDAC.
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