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KDM5D inhibit epithelial-mesenchymal transition of gastric cancer through demethylation in the promoter of Cul4A in male |
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| Authors: | Xudong Shen Kewei Hu Guilian Cheng Liming Xu Zhengrong Chen Peng Du Zhixiang Zhuang |
| Institution: | 1. Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
Xudong Shen and Kewei Hu contributed equally to this study.;2. Department of gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, China Xudong Shen and Kewei Hu contributed equally to this study.;3. Department of gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, China;4. Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China;5. Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China |
| Abstract: | Gastric cancer is one of the top causes of cancer-related death around the world, and poor prognosis of gastric cancer is due to the lack of early detection and effective treatment especially in male. Here, we first revealed the role of histone lysine-specific demethylase 5D (KDM5D) in gastric cancer in male. KDM5D was associated with the metastasis of gastric cancer because of its critical role in the epithelial-mesenchymal transition of gastric cancer cells. Downregulation of KDM5D in gastric cancer cells significantly increase the number of migrated or invaded cells due to the increasing expressions of mesenchymal markers. Downregulation of KDM5D also promotes tumor formation of gastric cancer cell in vivo. For mechanism, downregulation of KDM5D could inhibit the demethylation in the promoter of CUL4A, which lead to the increasing expression of ZEB1 and decreasing expressions of p21 and p53. Collectively, KDM5D performed its role in metastasis of gastric cancer through demethylation in the promoter of CUL4A, and it suggested us a novel target in gastric cancer treatment in male. |
| Keywords: | CUL4A epithelial-mesenchymal transition (EMT) gastric cancer (GC) histone lysine-specific demethylase 5D (KDM5D) |