WTAP is a prognostic marker of high-grade serous ovarian cancer and regulates the progression of ovarian cancer cells

Abstract

Hai-Lan Yu,1,2 Xu-Dong Ma,1,2 Jin-Fei Tong,1,2 Jian-Qiong Li,1,2 Xiao-Jing Guan,1,2 Jian-Hua Yang1,21Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, People’s Republic of ChinaBackground: The Wilms’ tumor suppressor WT1 is reported to work in a range of physiological processes at both transcriptional and posttranscriptional level. WT1-associating protein (WTAP), a nuclear protein co-localized with splicing factors, also plays a vital role in cellular function and cancer progression. However, little is known about the role of WTAP in ovarian cancer and the underlying mechanism.Materials and methods: To evaluate the expression of WTAP, multiple means were applied in clinical tissues, including immunohistochemistry, quantitative reverse transcriptase PCR (qRT-PCR), and Western blot. Two representative ovarian cancer cell lines (3AO and SKOV3) were used to assess the malignant influence of WTAP on proliferation, apoptosis, and migration. To explore its function, WTAP was additionally down-regulated by lentivirus.Results: High expression of WTAP in high-grade serous ovarian carcinoma (HGSOC) predicted a shorter overall survival (P<0.01). Furthermore, WTAP expression was higher in HGSOC, compared with that in normal ovary group (P<0.01), benign ovarian tumor group (P<0.01), and non-HGSOC group (P<0.05). In HGSOC, high expression of WTAP was significantly related with the lymph node metastasis (P<0.05). In ovarian cancer cell lines, cell proliferation and migration were considerably reduced after WTAP was down-regulated, while apoptotic rate was increased. Moreover, the effect of WTAP in 3AO and SKOV3 might be relevant with MAPK and AKT signaling pathways.Conclusion: WTAP is highly expressed in HGSOC, and indicates a worse survival outcome. Therefore, it is highly possible that WTAP has a prognostic implication in the patients of HGSOC. In addition, WTAP down-regulation also plays a tumor suppressor role in 3AO and SKOV3 cell lines.Keywords: WTAP, ovarian cancer, diagnosis, tumor suppression

Keywords

• WTAP
• ovarian cancer
• diagnosis
• tumor suppression