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

Abstract

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.

Circular PVT1 regulates cell proliferation and invasion via miR-149-5p/FOXM1 axis in ovarian cancer

“…CircRNAs have been found to be a type of key regulators in cancers. It has been found that circular PVT1 is a carcinogenic non-coding RNA and has important clinical significance in numerous carcinoma including ovarian cancer, gastric cancer and thyroid cancer [33][34][35][36][37][38][39][40][41][42]. For example, reduced circular RNA circPVT1 retarded gastric cancer growth via microRNA-3666-mediated reduced SIRT7 level [43].…”

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

“…Several circRNAs (such as circEPSTI1, circGFRA1, circ0051240, circPIP5K1A, circPVT1 and circABCB10) have been found to increase the proliferative and invasive capacities of OC cells by acting as miRNA sponges [ 121 , 122 , 123 , 124 , 125 , 126 ]. Knockdown of circSMAD7 by short-hairpin RNA (shRNA) was associated with decreased cell proliferation, migration and invasion and with increased expression of KLF6 in CC cells [ 127 ].…”

CircPVT1 promotes gallbladder cancer growth by sponging miR-339-3p and regulates MCL-1 expression

“…CircPVT1 is generated from exon 2 of the PVT1 gene and has been widely recognized to act as oncogene in several tumors [ 12 ]. In epithelial ovarian cancer, researchers revealed that circPVT1 expression was upregulated and enhanced cell proliferation but inhibited cell apoptosis through sponging microRNA-149 [ 13 ]. In gastric cancer (GC), circPVT1 contributed to paclitaxel resistance of GC cells through regulating ZEB1 expression by sponging to miR-124-3p [ 14 ].…”