Circ_0000231 promotes paclitaxel resistance in ovarian cancer by regulating miR-140/RAP1B

Am J Cancer Res. 2023 Mar 15;13(3):872-885. eCollection 2023.

Abstract

Circular RNAs (circRNAs) are identified as vital regulators in a variety of cancers. However, the involvement of circ_0000231 in paclitaxel (PTX) resistant ovarian cancer (OC) remains unclear. In this study, we examined the levels of circ_0000231, microRNA-140 (miR-140) and RAP1B in PTX-resistant OC tissues and cells and found that circ_0000231 and RAP1B levels were increased, while miR-140 level was decreased in these cells. Depletion of circ_0000231 could inhibit the resistance, proliferation, invasion, migration and EMT and promoted the apoptosis of PTX-resistant OC cells. The opposite effects were observed by overexpression of circ_0000231. Furthermore, the effect of circ_0000231 on the PTX sensitivity of OC cells was investigated by using xenograft tumor models, and circ_0000231 knockdown increased PTX sensitivity of OC in vivo. Mechanistically, we demonstrated that circ_0000231 acted as a sponge for miR-140, and RAP1B was the target gene of miR-140. Taken together, these data indicated that circ_0000231 was a key molecule required for the growth, migration, and PTX-resistance of OC cells and was involved in EMT. Knockdown of circ_000231 suppressed PTX-resistant OC progression via regulating miR-140/RAP1B signaling pathway. circ_0000231 might play vital roles in the tumorigenesis and chemoresistance of OC.

Keywords: Ovarian cancer; RAP1B; chemoresistance; circ_0000231; miR-140; paclitaxel.