Department of Histology and Embryology, Medical School of Hunan University of Chinese Medicine, Changsha, China.
Department of Orthopedics, The Third Xiangya Hospital of Central South University, Changsha, China.
J Obstet Gynaecol Res. 2020 Apr;46(4):625-635. doi: 10.1111/jog.14190. Epub 2020 Feb 11.
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.
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.
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.
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.
本研究旨在探讨环状 RNA PVT1(circ-PVT1)对卵巢上皮性癌(EOC)细胞增殖和凋亡的影响,更重要的是,鉴定 EOC 中 circ-PVT1 的靶微小 RNA(miRNA)。
检测 EOC 细胞系和非恶性对照细胞中的 circ-PVT1 表达。在 circ-PVT1 过表达处理的 CAOV3 细胞和 circ-PVT1 敲低处理的 SKOV3 细胞中检测细胞增殖、凋亡和候选靶 miRNA(miR-149、miR-183 和 miR-194)表达。此外,将 miR-149 过表达和 miR-149 敲低质粒分别转染到 circ-PVT1 失调的 CAOV3 细胞和 SKOV3 细胞中,检测细胞增殖和凋亡。
与人类正常卵巢表面上皮细胞系(HOSEpiC)相比,人卵巢上皮性癌细胞系(CAOV3、SKOV3、SNU119 和 OVCAR3)中 circ-PVT1 的表达增加。在 SKOV3 细胞中,circ-PVT1 敲低可降低细胞增殖,但在 48 小时时增加细胞凋亡率。在 CAOV3 细胞中,circ-PVT1 过表达可增加细胞增殖,但在 48 小时时降低细胞凋亡率。此外,circ-PVT1 在 SKOV3 和 CAOV3 细胞中负调控 miR-149,但不调控 miR-183 或 miR-194。挽救实验表明,在 circ-PVT1 敲低处理的 SKOV3 细胞中,miR-149 敲低增加细胞增殖并降低凋亡,而在 circ-PVT1 过表达处理的 CAOV3 细胞中,miR-149 过表达降低细胞增殖并增强凋亡。
circ-PVT1 通过海绵吸附 miR-149 增强 EOC 细胞增殖并抑制细胞凋亡,提示 circ-PVT1 可能作为 EOC 的治疗靶点。