1. Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China;
2. Shanghai Key Laboratory of Gynecologic Oncology, Focus Construction Subject of Shanghai Education Department, Shanghai;
3. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA;
4. Cancer Institute, Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China;
5. Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China.
*These authors contributed equally to this work.
Ovarian cancer is the fifth common cause of death in woman worldwide. The tripartite motif-containing (TRIM) proteins consist of more than 70 known protein members. Studies have showed that TRIM proteins are involved in cancer and play important roles in cancer cell proliferation, migration, adhesion and metastasis. Recent studies have indicated that TRIM59, as a putative ubiquitin ligase, is up-regulated in some cancers and associated with poor prognosis of gastric cancer. However, the exact roles of TRIM59 in ovarian cancer are still unknown. In this study, we found that TRIM59 expression was increased and positively associated with histological grades (P = 0.000), FIGO stages (P = 0.016), and metastasis (P = 0.027) in ovarian cancer. A integrative data analysis tool revealed that ovarian cancer patients with high TRIM59 expression were correlated with more unfavorable overall and progression-free survival than the rest patients with low TRIM59 expression (P = 0.0024 and P = 7.5×10-6, respectively). Based on the finding in the clinical data, we performed a series of cell line and animal experiments, and found that TRIM59 knockdown could significantly inhibit the ovarian cancer cell proliferation, clone formation, and invasion in vitro and the ovarian cancer growth of the subcutaneous and orthotopic implantation in vivo. Furthermore, TRIM59 was found to interact with Annexin A2 and induce Annexin A2 expression. Our data imply that TRIM59 can serve as a promising prognostic marker and a potential therapeutic target.
Keywords: TRIMP59, Tissue microarray, Ovarian cancer, Metastasis, Annexin A2