J Cancer 2019; 10(11):2480-2487. doi:10.7150/jca.29489 This issue
1. Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China
2. Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, Shanghai 200032
3. Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China
Objective: Recently, accumulating evidence has indicated that the 3' untranslated regions (3'UTRs) of protein coding genes play critical roles in the progression of various cancers, including ovarian cancer. This study is aimed to identify the potential role of SNAI2-3'UTR in ovarain cancer progression.
Study Design: First, we tried to explore the clinical significance of SNAI2 in ovarian cancer using TCGA and GSE26712 dataset. Then, gain-of-function studies were performed to establish the role of SNAI2-3'UTR in invasion and migration of ovarian cancer cells. Finally, efforts were made to identify the downstream targets of SNAI2-3'UTR.
Results: Our data indicated that the expression of SNAI2 was significantly correlated with FIGO stage (P=0.015) and lymphatic invasion status (P=0.004), whereas not with age(P>0.05) and histological grade(P>0.05). Patients with higher SNAI2 expression had a shorter overall survival (OS) in both TCGA dataset (P=0.039, HR=1.54(1.02-2.33)) and GSE26712 dataset (P=0.0017, HR=1.77(1.24-2.54)). Functional studies revealed that SNAI2-3'UTR promoted the invasion of both OVCA433 and SKOV-3 cells without significantly affecting their migratory abilities. MARCKS, which was also involved in the invasion of ovarian cancer cells, was identified as a potential downstream target of SNAI2-3'UTR. SNAI2-3'UTR may function as a ceRNA to upregulate MARCKS expression in ovarian cancer.
Conclusion: In conclusion, our study demonstrated that SNAI2-3'UTR cloud promote the invasion of ovarian cancer cells by upregulating MARCKS expression, which proposed a new mechanism by which SNAI2 contributed to progression of ovarian cancer.
Keywords: Ovarian cancer, SNAI2, MARCKS, 3' untranslated regions, Invasion