Circular RNA PVT1 enhances cell proliferation but inhibits apoptosis through sponging microRNA‐149 in epithelial ovarian cancer

• Published in: The journal of obstetrics and gynaecology research Vol. 46; no. 4; pp. 625 - 635
• Main Authors: Sun, Xiaofeng, Luo, Ling, Gao, Yuqiang
• Format: Journal Article
• Language: English
• Published: Kyoto, Japan John Wiley & Sons Australia, Ltd 01-04-2020; Wiley Subscription Services, Inc
• Subjects: Apoptosis; Apoptosis - genetics; Carcinoma, Ovarian Epithelial - genetics; cell apoptosis; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - genetics; Circular RNA; circular RNA‐PVT1; Epithelial cells; epithelial ovarian cancer; Female; Humans; MicroRNAs; MicroRNAs - genetics; microRNA‐149; miRNA; Ovarian cancer; Ovarian Neoplasms - genetics; Plasmids; RNA, Circular - genetics; RNA, Long Noncoding - genetics; cell apoptosis; circular RNA-PVT1; epithelial ovarian cancer; cell proliferation; microRNA-149
• ISSN: 1341-8076; 1447-0756
• DOI: 10.1111/jog.14190

Aim
This study aimed to investigate the influence of circular RNA PVT1 (circ‐PVT1) on epithelial ovarian cancer (EOC) cell proliferation and apoptosis, more importantly, to identify the target microRNAs (miRNA) of circ‐PVT1 in EOC.
Methods
Circ‐PVT1 expression in EOC cell lines and nonmalignant control cells was detected. Cell proliferation, apoptosis and candidate target miRNA (miR‐149, miR‐183 and miR‐194) expressions were detected in circ‐PVT1 overexpression treated CAOV3 cells and circ‐PVT1 knock‐down treated SKOV3 cells. Furthermore, miR‐149 overexpression and miR‐149 knock‐down plasmids were transfected into circ‐PVT1 dysregulated CAOV3 cells and SKOV3 cells, respectively, and cell proliferation as well as apoptosis were detected.
Results
Circ‐PVT1 expression was increased in human EOC cell lines (CAOV3, SKOV3, SNU119 and OVCAR3) compared to human normal ovary surface epithelial cell line (HOSEpiC). In SKOV3 cells, cell proliferation was reduced at 48 and 72 h but cell apoptosis rate was increased at 48 h by circ‐PVT1 knock‐down. In CAOV3 cells, cell proliferation was increased at 48 and 72 h but cell apoptosis rate was decreased at 48 h by circ‐PVT1 overexpression. Besides, circ‐PVT1 negatively regulated miR‐149 but not miR‐183 or miR‐194 in SKOV3 and CAOV3 cells. Rescue experiments showed that miR‐149 knock‐down increased cell proliferation but decreased apoptosis in circ‐PVT1 knock‐down treated SKOV3 cells, while miR‐149 overexpression reduced cell proliferation but enhanced apoptosis in circ‐PVT1 overexpression treated CAOV3 cells.
Conclusion
Circ‐PVT1 enhances cell proliferation but inhibits cell apoptosis through sponging miR‐149 in EOC cells, which suggests that circ‐PVT1 may serve as a treatment target in EOC.