机构：[1]Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China[2]Department of Genetics and Eugenics, Maternity and Child Care Center of Qinghuangdao, Qinghuangdao 066000, China[3]Genetic Diagnosis Center, First People's Hospital of Yunnan Province, Yunnan 650032, China门急诊片医学遗传科云南省第一人民医院[4]Department of Clinical Oncology, Faculty of Medicine, The University of Hong Kong, Hong Kong, China[5]State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China[6]Key Laboratory of Medical Genetics, Harbin Medical University, Heilongjiang Higher Education Institutions, Harbin 150081, China
Previous studies have shown that the oncogene SEI1 is highly expressed in ovarian carcinomas, and promoting genomic instability. However, the molecular mechanism of SEI1 in promoting genomic instability remains unclear. We observed SEI1 overexpression in 30 of 46 cases of ovarian cancer compared to non-tumor tissues and the overexpression of SEI1 was positively associated with the tumor FIGO stage. Our functional studies revealed that overexpression of SEI1 could induce genomic instability and increased DNA strand breaks. In contrast, SEI1 co-localized with gamma H2AX and phosphorylated ATM and DNAPKcs in the nucleus. Furthermore, we found that overexpression of Sal induced translocation of the SEI1 protein from the cytoplasm to the nucleus; ATM and DNAPKcs were associated with the cytoplasm-to-nucleus translocation of SEI1 To further prove the correlation between the DNA damage response (DDR) and SEI1, we knocked down SEI1 expression in SEI1-transfected ovarian cancer cell lines. The expression of DDR proteins was significantly downregulated, and the number of micronuclei was significantly decreased. Together, these results define a new mechanism of SEI1 in the regulation of genomic stability and in the malignant progression of ovarian cancer. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
基金：
Programme of Innovative Research Team in University [IRT1230]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81272868, 81672572, 81372784]; New Century Support Programme for the Excellent Scholar, Ministry of Education of ChinaMinistry of Education, China [NCET-13-0758]; Heilongjiang Province Natural Science Foundation for Youths [QC2012C017]
第一作者机构：[1]Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China
通讯作者：
通讯机构：[1]Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China[6]Key Laboratory of Medical Genetics, Harbin Medical University, Heilongjiang Higher Education Institutions, Harbin 150081, China[*1]157 Baojian Road, Nangang District, Harbin 150081,China
推荐引用方式(GB/T 7714)：
You Jia,Liu Jia,Bao Yantao,et al.SEI1 induces genomic instability by inhibiting DNA damage response in ovarian cancer[J].CANCER LETTERS.2017,385:271-279.doi:10.1016/j.canlet.2016.09.032.
APA：
You, Jia,Liu, Jia,Bao, Yantao,Wang, Liqun,Yu, Yang...&Jin, Yan.(2017).SEI1 induces genomic instability by inhibiting DNA damage response in ovarian cancer.CANCER LETTERS,385,
MLA：
You, Jia,et al."SEI1 induces genomic instability by inhibiting DNA damage response in ovarian cancer".CANCER LETTERS 385.(2017):271-279
医学