CircSERPINE2 Induces Platinum Resistance in Ovarian Cancer via the miR-513a-5p/miR-526b-3p/SEMA7A Axis.
TL;DR
CircSERPINE2 promotes platinum resistance in OC cells and induces an immunosuppressive environment through the miR-513a-5p/miR-526b-3p/SEMA7A axis, highlighting its potential as a target for overcoming platinum resistance in OC.
Abstract
INTRODUCTION Ovarian cancer (OC) is the third most aggressive gynecological malignancy worldwide, and platinum resistance is a common malignant feature of OC associated with poor clinical prognosis. Circular RNA (circRNA) has been reported in many tumor progressions, including drug resistance. In this study, a new circRNA that mediates OC progression by acting as a ceRNA was identified.
Methods
Through high-throughput transcriptome sequencing and bioinformatic analyses, the CircSERPINE2/miR-513a-5p/miR-526b-3p/SEMA7A axis was identified as a potential key factor in the development of platinum resistance in OC. CCK-8, colony formation assay, and flow cytometry confirmed the role of CircSERPINE2 in regulating platinum resistance in OC. Relevant patents were cited by the China National Intellectual Property Administration (CNIPA).
Results
In OC cells and subcutaneous xenograft tumors, downregulation of CircSERPINE2 was associated with elevated expression of miR-513a-5p/miR-526b-3p, inactivation of the SEMA7A/ IL-6 pathway, and reduced tumor size following platinum treatment. Furthermore, the CircSERPINE2/SEMA7A axis mediated IL-6 autocrine in OC cells and significantly decreased platinum-induced apoptosis. Moreover, the CircSERPINE2/SEMA7A axis promoted M2 polarization of macrophages in the tumor microenvironment, which in turn impaired platinum sensitivity in ovarian cancer cells.
Discussion
Given that circRNAs can act as promising clinical diagnostic biomarkers and therapeutic targets, the development of circRNA vaccine nanocomposites represents a novel and promising therapeutic strategy to potentiate tumor-killing efficacy when combined with chemotherapy regimens. On this basis, our subsequent research will focus on the rational design and development of a tailored nano-drug delivery system for this application.
Conclusion
CircSERPINE2 promotes platinum resistance in OC cells and induces an immunosuppressive environment through the miR-513a-5p/miR-526b-3p/SEMA7A axis, highlighting its potential as a target for overcoming platinum resistance in OC.