CircRhoC promotes tumorigenicity and progression in ovarian cancer by functioning as a miR‐302e sponge to positively regulate VEGFA

Abstract

Ovarian cancer is a leading cause of deaths due to gynaecological malignancy. While endogenous non‐coding circular RNAs (circRNAs) in cancer have attracted attention, their roles in ovarian cancer are not known. We used qRT‐PCR to quantify expression of circRhoC in ovarian cancer tissues and normal tissues. The effects of overexpressing or destruction of circRhoC on the phenotype of ovarian cancer cells were assessed both in vitro and in vivo. Dual‐luciferase reporter assay assesses the microRNA sponge function of circRhoC. Western blotting was used to confirm the effects of circRhoC and microRNA on target gene expression. Our results showed that circRhoC was significantly up‐regulated in ovarian cancer tissues compared to normal ovarian tissues. Overexpression of circRhoC in CAOV3 ovarian cancer cell increased cell viability, migration and invasion ability; destroying circRhoC in A2780 had the opposite effects and inhibited ovarian tumour cell A2780 dissemination in the peritoneum in vivo. We confirmed circRhoC functions as a sponge for miR‐302e to positively regulate VEGFA; FISH experiments showed that circRhoC could co‐focal with miR‐302e; besides, overexpression of miR‐302e reversed the ability of circRhoC to positively regulate VEGFA, and what's more, RIP assay showed that circRhoC could directly bind with VEGFA; besides, VEGFA expression level in ovarian cancer tissues was positively associated with circRhoC expression. In conclusion, the oncogenic effect of RhoC in ovarian cancer is at least in part due to circRhoC, which functions not only as a miR‐302e sponge to positively regulate VEGFA protein expression, but may also directly bind and modulate VEGFA expression.

The Expression, Functions and Mechanisms of Circular RNAs in Gynecological Cancers

“…Suppression of circRhoC with shRNA significantly attenuated cell migration and invasion in vitro, and inhibited the intraperitoneal dissemination of OC cells in vivo [140]. By performing mechanistic analysis, the same study indicated that circRhoC can serve as a sponge for miR-302e to upregulate the expression of VEGF-A, which potentially promotes OC angiogenesis and metastasis [140].…”

“…Vascular endothelial growth factor (VEGF-A) has a prominent role in tumor angiogenesis [139]. CircRhoC, a circRNA derived from the RhoC mRNA, was overexpressed in OC tissues relative to normal ovarian tissues, and higher circRhoC expression was detected in advanced-stage tumors compared with early-stage tumors [140]. Suppression of circRhoC with shRNA significantly attenuated cell migration and invasion in vitro, and inhibited the intraperitoneal dissemination of OC cells in vivo [140].…”

“…CircRhoC, a circRNA derived from the RhoC mRNA, was overexpressed in OC tissues relative to normal ovarian tissues, and higher circRhoC expression was detected in advanced-stage tumors compared with early-stage tumors [140]. Suppression of circRhoC with shRNA significantly attenuated cell migration and invasion in vitro, and inhibited the intraperitoneal dissemination of OC cells in vivo [140]. By performing mechanistic analysis, the same study indicated that circRhoC can serve as a sponge for miR-302e to upregulate the expression of VEGF-A, which potentially promotes OC angiogenesis and metastasis [140].…”

MicroRNA‐148a‐3p inhibits cancer progression and is a novel screening biomarker for gastric cancer

“…microRNAs (miRNAs) are a group of small noncoding RNAs which could regulate the post‐transcription expression level of their target genes 11,12 . Numerous studies have reported the close correlation between the aberrant expression of certain miRNAs and cancer progression 13,14 . For instance, miR‐193a‐3p was reported to regulate cisplatin resistance in CD44(+) gastric cancer cells 15 .…”

CircNOLC1 promotes epithelial ovarian cancer tumorigenesis and progression by binding ESRP1 and modulating CDK1 and RhoA expression

“…In addition, our previous research reported that circRhoC functions not only as a miR-302e sponge to positively regulate VEGFA protein expression, but may also directly bind and modulate VEGFA expression to promote ovarian cancer development. [22]. Using bioinformatic analysis, we found that circNOLC1 could also bind with proteins such as ESRP1.…”