TRIM59 Is a Novel Marker of Poor Prognosis and Promotes Malignant Progression of Ovarian Cancer by Inducing Annexin A2 Expression

• Published in: International journal of biological sciences Vol. 14; no. 14; pp. 2073 - 2082
• Main Authors: Wang, You, Zhou, Zhicheng, Wang, Xinran, Zhang, Xuping, Chen, Yansu, Bai, Jin, Di, Wen
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 01.01.2018; Ivyspring International Publisher
• Subjects: Animals; Annexin A2 - genetics; Annexin A2 - metabolism; Cancer; Cell growth; Cell Line, Tumor; Cell migration; Cell proliferation; Cell Proliferation - genetics; Cell Proliferation - physiology; Data analysis; Data processing; Female; Gastric cancer; Gene Expression Regulation, Neoplastic - genetics; Gene Expression Regulation, Neoplastic - physiology; Humans; Immunohistochemistry; Immunoprecipitation; Implantation; Intracellular Signaling Peptides and Proteins; Medical prognosis; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metalloproteins - genetics; Metalloproteins - metabolism; Metastases; Metastasis; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Patients; Prognosis; Proteins; Real-Time Polymerase Chain Reaction; Research Paper; Signal Transduction; Surgical implants; Therapeutic applications; Tripartite Motif Proteins; Ubiquitin; Ubiquitin-protein ligase; Xenograft Model Antitumor Assays; Tissue microarray; TRIMP59; Annexin A2; Metastasis; Ovarian cancer
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.28757

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 ( = 0.000), FIGO stages ( = 0.016), and metastasis ( = 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 ( = 0.0024 and = 7.5×10 , 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 and the ovarian cancer growth of the subcutaneous and orthotopic implantation . 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.