Identification of WTAP-related genes by weighted gene co-expression network analysis in ovarian cancer
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RESEARCH
Open Access
Identification of WTAP-related genes by weighted gene co-expression network analysis in ovarian cancer Jing Wang1,2†, Jing Xu1,2†, Ke Li1†, Yunke Huang1, Yilin Dai1, Congjian Xu1,2* and Yu Kang1,2*
Abstract Background: Wilms tumor 1 associated protein (WTAP) modulates other genes via transcriptional and posttranscriptional regulation, in particular, by acting as a N6-methyladenosine writer or binding to the 3’UTR of mRNA, and promotes a variety of tumuors. However, the roles and mechanisms of WTAP in ovarian cancer are unknown. Results: In this study, using univariate Cox analysis and online CPTA analysis, we found that WTAP was a poor prognostic factor for ovarian cancer, and its protein expression level was higher in ovarian cancer than in normal tissue. Functionally, WTAP promoted the proliferation, invasion, and migration capability of ovarian cancer, according to the results of real time cellular analysis (RTCA), EdU cell proliferation assay, transwell assay. Subsequently, we identified a module containing 133 genes that were carefully related to WTAP expression through weighted gene co-expression network analysis (WGCNA). By calculating the hazard ratios of these genes and comparing their differences in the WTAP high-expression group and the low-expression group, we observed that there was a significant positive correlation between WTAP and two poor survival-related genes, family with sequence similarity 76 member A (FAM76A) and HBS1 like translational GTPase (HBS1L), which was also verified by quantitative real-time PCR in SKOV3 and A2780 cells. Conclusion: WTAP functions as an oncogenic factor that promotes the progression of ovarian cancer in which WTAP-HBS1L/FAM76A axis may be involved. Our study indicates the potential role of WTAP in prognostic biomarker and therapeutic target for ovarian cancer. Keywords: Ovarian cancer, Progression, WTAP, WGCNA, HBS1L, FAM76A
Introduction Ovarian cancer is the most lethal malignancy of the female reproductive tract, with a 5 year survival rate of only 29% in the advanced stage, and approximately 75% of cases are diagnosed in that stage [1]. Primary debulking surgery followed by platinum-based combination chemotherapy has become the standard treatment in advanced ovarian cancer since the 1980s [2]. However, * Correspondence: [email protected]; [email protected] † Jing Wang, Jing Xu and Ke Li contributed equally to this work. 1 Obstetrics and Gynecology Hospital, Fudan University, No.419, Fangxie Road, Shanghai 200011, People’s Republic of China Full list of author information is available at the end of the article
during the past years, patients with high-grade serous ovarian cancer have experienced little improvement in overall survival, and standard treatment has not advanced beyond the previous one [3]. Therefore, investigation of the mechanisms of ovarian cancer progression is needed, which may provide insight for new treatment targets to improve ovarian cancer prognosis. N6-methyladenosine (m6A) modification, the most common rever
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