Zai-Fa Hong1, Wen-Qing Zhang2, Shuang-Jia Wang3, Si-Yang Li4, Jin Shang4, Fan Liu5, Dong-Yan Shen6. 1. Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong, China; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 2. Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China. 3. Department of Hepato-Biliary-Pancreatic and Vascular Surgery, the First Affiliated Hospital, Xiamen University, Xiamen 361003, Fujian Province, China. 4. Biobank, The First Affiliated Hospital, Xiamen University, Xiamen 361003, Fujian Province, China. 5. Reproductive Health Research, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China. Electronic address: liufan@xmu.edu.cn. 6. Biobank, The First Affiliated Hospital, Xiamen University, Xiamen 361003, Fujian Province, China. Electronic address: liufan@xmu.edu.cn.
Abstract
OBJECTIVES: Modification of lysine 4 on histone H3 methylation by SET1 and MLL family methyltransferase complexes is tightly linked to cancer progression. DPY30 is an important subunit of SET1 and MLL complexes, however, its expression and roles in cancer progression was little known, especially in cholangiocarcinoma (CCA). MATERIALS AND METHODS: The Q-PCR and IHC were performed to detect the levels of DPY30 mRNA and protein in CCA tissues. Effect of DPY30 knockdown on the proliferation of CCA cells was detected by MTS and colony formation, and cell cycle distribution was analyzed by flow cytometer. The glucose uptake, lactate release and ATP production assays were performed to detect the glycolysis of CCA cells. RESULTS: The level of DPY30 mRNA and protein in CCA tissues were all significantly higher than that of pericancer tissues, and its upregulation was closely associated with pathological differentiation, tumor size, and TNM stage. In addition, Kaplan-Meier analysis of overall survival revealed that DPY30 upregulation was significantly associated with poor survival, and univariate and multivariate analysis indicated that it was an independently prognosis factor in CCA patients. Moreover, DPY30 knockdown inhibited in-vitro growth and induced cell cycle arrest at G2/M and decreased glycolysis in CCA cells. CONCLUSIONS: DPY30 upregulation may promote the development of CCA and was associated with the aggressive malignant behavior and poor survival outcome of CCA patients. DPY30 might serve as a potential novel target for treatment of CCA patients.
OBJECTIVES: Modification of lysine 4 on histone H3 methylation by SET1 and MLL family methyltransferase complexes is tightly linked to cancer progression. DPY30 is an important subunit of SET1 and MLL complexes, however, its expression and roles in cancer progression was little known, especially in cholangiocarcinoma (CCA). MATERIALS AND METHODS: The Q-PCR and IHC were performed to detect the levels of DPY30 mRNA and protein in CCA tissues. Effect of DPY30 knockdown on the proliferation of CCA cells was detected by MTS and colony formation, and cell cycle distribution was analyzed by flow cytometer. The glucose uptake, lactate release and ATP production assays were performed to detect the glycolysis of CCA cells. RESULTS: The level of DPY30 mRNA and protein in CCA tissues were all significantly higher than that of pericancer tissues, and its upregulation was closely associated with pathological differentiation, tumor size, and TNM stage. In addition, Kaplan-Meier analysis of overall survival revealed that DPY30 upregulation was significantly associated with poor survival, and univariate and multivariate analysis indicated that it was an independently prognosis factor in CCApatients. Moreover, DPY30 knockdown inhibited in-vitro growth and induced cell cycle arrest at G2/M and decreased glycolysis in CCA cells. CONCLUSIONS:DPY30 upregulation may promote the development of CCA and was associated with the aggressive malignant behavior and poor survival outcome of CCApatients. DPY30 might serve as a potential novel target for treatment of CCApatients.