Hsa_circ_0000585 promotes chemoresistance to cis-platin in epithelial cells of ovarian cancer by modulating autophagy

by Selleckchem | Jan 19 2024

Background: Chemoresistance, i.e., resistance to cisplatin (DDP), has been a major obstacle to ovarian cancer treatment. It has been found that circular RNAs (circRNAs) play vital roles in the tumorigenesis various cancers by regulating autophagy, while few studies focusing on cisplatin-resistance ovarian cancer (CROC).

Methods: The expressions of the circRNAs were detected by qRT-PCR. Short hairpin RNA targeting circRNA was used to explore the biological functions of the circRNA. Cell viability, autophagic flux, immunofluorescence, and xenograft tumors experiments were performed to further illustrate the underlying mechanisms.

Results: Hsa_circ_0000585 was increased in cisplatin-resistant SKOV3/DDP cells. Stably knocking down hsa_circRNA_0000585 expression in SKOV3/DDP cells was established by RNA interference. We found that downregulation of hsa_circ_0000585 significantly enhanced the sensitivity of DDP/SkOV3 cells to DDP. In vivo study, hsa_circRNA_0000585 knockdown significantly decreased tumor volume in nude mice. Under the measurements of western blot and cellular immunofluorescence, hsa_circ_0000585 knockdown significantly inhibited the expression of Beclin1 and P62, indicating the autophagic flux was inhibited. Administrations with autophagic inhibitor "Chloroquine (CQ)" and autophagy activator "QX77" further confirmed that hsa_circ_0000585 knockdown resulted in autophagy inhibition.

Conclusions: Overall, this study provided a new insight into the role of circRNAs in the mechanism of DDP-resistance in ovarian cancer. Hsa_circRNA_0000585 may be promising therapeutic targets for the enhancement of the sensitivity of ovarian cancer cells to cisplatin-mediated chemotherapy.

Comments:

This research you're summarizing sounds quite promising in the realm of understanding and potentially overcoming chemoresistance in ovarian cancer, specifically focusing on the role of circular RNAs (circRNAs) in cisplatin resistance.

The study identified hsa_circ_0000585 as being increased in cisplatin-resistant SKOV3/DDP cells. Knocking down this particular circRNA enhanced the sensitivity of these cells to cisplatin treatment. Additionally, in vivo experiments showed a decrease in tumor volume in mice when hsa_circRNA_0000585 was knocked down. The study delved into the mechanisms behind this, finding that hsa_circ_0000585 knockdown inhibited autophagic flux, as evidenced by changes in the expression of autophagy-related proteins like Beclin1 and P62. Further confirmation through the use of autophagic inhibitors and activators supported the conclusion that hsa_circ_0000585 knockdown resulted in autophagy inhibition.

The findings suggest a potential therapeutic avenue by targeting hsa_circRNA_0000585 to enhance the sensitivity of ovarian cancer cells to cisplatin-based chemotherapy. This could offer a promising strategy in overcoming chemoresistance, which is a significant challenge in ovarian cancer treatment.

This research could potentially pave the way for further exploration and development of targeted therapies focusing on circRNAs to improve the effectiveness of cisplatin treatment in ovarian cancer patients.