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

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.

Sun X ，Luo L ，Gao Y 《-》

Circular RNA ITCH suppresses proliferation and promotes apoptosis in human epithelial ovarian cancer cells by sponging miR-10a-α.

Luo L ，Gao YQ ，Sun XF 《-》

Circular RNA ABCB10 promotes cell proliferation and invasion, but inhibits apoptosis via regulating the microRNA‑1271‑mediated Capn4/Wnt/β‑catenin signaling pathway in epithelial ovarian cancer.

Lin X ，Chen Y ，Ye X ，Xia X ... -  《-》

Circ-PGAM1 promotes malignant progression of epithelial ovarian cancer through regulation of the miR-542-3p/CDC5L/PEAK1 pathway.

Epithelial ovarian cancer (EOC) is the most common ovarian malignant cancer. Circular RNA is a type of endogenous noncoding RNA and is considered as a novel regulatory molecule in the development and progression of tumors. This study investigated the expression and functions of a circular RNA, circular-phosphoglycerate mutase 1 (circ-PGAM1), in EOC tissues and cells. The expression of circ-PGAM1 and miR-542-3p in EOC was analyzed using quantitative RT-PCR. Immunohistochemistry and western blot were performed to confirm the localization and expression of cell division cycle 5-like (CDC5L) and pseudopodium enriched atypical kinase 1 (PEAK1) in EOC tissues. Cell lines (CAOV3 and OVCAR3) overexpressing or silencingcirc-PGAM1 and miR-542-3p were established to explore the functions of circ-PGAM1 and miR-542-3p in ovarian cancer cells. Furthermore, dual-luciferase reporter assay was performed to study the interactions between circ-PGAM1 and miR-542-3p and between miR-542-3p and CDC5L. CCK-8, transwell, and flow cytometry were used to study the effect of circ-PGAM1 and miR-542-3p on cell biological behaviors including proliferation, migration, invasion, and apoptosis. The interaction between CDC5L and the PEAK1 gene promoter was confirmed using chromatin immunoprecipitation (ChIP). Circ-PGAM1 was upregulated in EOC tissues, whereas linear PGAM1 was not deregulated in EOC tissues. Silencing of circ-PAGM1 inhibited proliferation, migration, and invasion of ovarian cancer cells and promoted cell apoptosis. MiR-542-3p was downregulated in EOC tissues, and miR-542-3p overexpression inhibited malignant progression of ovarian cancer cells. Circ-PGAM1 directly interacted with miR-542-3p, with mutual negative feedback between them. CDC5L was a direct target of miR-542-3p and played an oncogenic role in ovarian cancer cells. Furthermore, the CDC5L protein binds directly to the PEAK1 promoter to promote its transcription. PEAK1 overexpression activated ERK1/2 and JAK2 signaling pathways and promoted malignant biological behaviors of ovarian cancer cells. Circ-PAGM1 silencing combined with miR-542-3p overexpression played the greatest anticancer role in vivo. The circ-PGAM1/miR-542-3p/CDC5L/PEAK1 pathway played an important role in the progression of ovarian cancer and might be a novel therapeutic target for ovarian cancer.

Zhang C ，Li Y ，Zhao W ，Liu G ，Yang Q ... -  《Cancer Medicine》

Circular RNA ABCB10 correlates with advanced clinicopathological features and unfavorable survival, and promotes cell proliferation while reduces cell apoptosis in epithelial ovarian cancer.

Chen Y ，Ye X ，Xia X ，Lin X ... -  《-》