Abstract 1399
Background
Histone methyltransferase G9a is up-regulated in a wide variety of human tumors. The aims of this study are to clarify G9a expression in tumor tissues and its adjacent normal tissues of gastric cancer, to investigate the effect of G9a on tumor invasion and metastasis of gastric cancer by up-regulating and down-regulating the expression of G9a in gastric cancer cells, and to validate it in animal model.
Methods
IHC was used to detect the expression of G9a in gastric cancer tissues and its adjacent non-tumor tissues and to analyze the relationship between G9a and clinicopathological parameters. After overexpressing or knock-down G9a stable gastric cancer cell lines were constructed, the effect of G9a on tumor invasion and metastasis of gastric cancer cells was detected by transwell assay, ankylosis resistance assay, soft agar formation assay and adhesion assay, nude mice model of cell peritoneal transplantation used to validate the in vitro results. The expression of related pathway gene was detected by WB, the interaction between the protein and the promoter region was detected by double luciferase reporter assay and ChIP and Co-IP was used to detect the interaction between proteins.
Results
G9a highly expressed in GC tissues. G9a expression level was correlated with advanced stage and shorter overall survival. Silencing G9a attenuate the peritoneal metastasis-relevant traits activities of GC cells, ectopic overexpression of G9A contributes to promote tumor metastasis. G9a expression can be induced by Reg IV via p-erk/p-SP1 pathway. SP1 directly binds to G9A promoter and promote its expression. G9a can form a transcriptional activator complex with P300 and GR to participate in ITGB3 expression induced by DEX. G9a participates in ITGB3 expression induced by DEX was independent on the SET domain and methyltransferase activity of G9a.
Conclusions
The expression of G9a in gastric cancer was significantly up-regulated. Overexpression of G9a in gastric cancer cells promoted tumor invasion and metastasis behavior of cancer cells and vise versa. G9a was involved in the process of tumor invasion and metastasis of gastric cancer through the regulation of ITGB3.
Clinical trial identification
Legal entity responsible for the study
Bingya Liu.
Funding
The National Natural Science Foundation of China, China (Nos. 91529302, 81572798, 81602160), The National Key Technology R&D Program of China (No. 2014BAI09B03.
Editorial Acknowledgement
This study was supported by grants from the National Natural Science foundation of China (Nos. 91529302, 81572798, 81602160), The National Key Technology R&D Program of China (No. 2014BAI09B03
Disclosure
All authors have declared no conflicts of interest.