1. Department of Gynaecology, Obstetrics and Gynaecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, China Shanghai 200011, China.
2. Department of Obstetrics and Gynaecology of Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
3. Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, 413 Zhaozhou Road, Shanghai 200011, China.
4. Department of Gynaecology, The First affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jianshe Road, Zhengzhou 471000, Zhengzhou 471000, China.
Antisense long noncoding RNAs serve as important regulators of protein-coding genes and contribute to tumorigenesis and metastasis. AGAP2-AS1, an antisense lncRNA transcribed from AGAP2, is involved in various cancer types. However, the clinical significance, biological roles and regulatory mechanisms of AGAP2-AS1 in epithelial ovarian cancer (EOC) have not been thoroughly elucidated to date. In this study, we demonstrated the expression pattern and biological roles of AGAP2-AS1 in EOC. Clinically, AGAP2-AS1 expression was decreased in EOC tissues compared to that in the controls. Low expression of AGAP2-AS1 was associated with advanced FIGO stage, high histological grade, serous subtype and lymph node metastasis in patients with EOC. AGAP2-AS1 inhibited cell migration, invasion and proliferation in vitro. AGAP2-AS1 suppressed tumor growth in vivo. Mechanistically, AGAP2-AS1 inhibited cell metastasis and proliferation by downregulating KRAS, FGFR4, and CTSK and suppressing epithelial-mesenchymal transition. In conclusion, we provide the first evidence for the tumor-suppressing effect of AGAP2-AS1 in EOC and demonstrate that AGAP2-AS1 may represent a promising therapeutic target for EOC patients.
Keywords: AGAP2-AS1, proliferation, metastasis, epithelial ovarian cancer