Recent patents on anti-cancer drug discovery · 2026
CircSERPINE2 Induces Platinum Resistance in Ovarian Cancer via the miR-513a-5p/miR-526b-3p/SEMA7A Axis.
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Niu Zhiyuan, Mo Yuqing, Yang Bikang, Zhang Mojian, Zhong Rui, Zhang Shufang, Yang Sheng, Peng Shuping
Аннотация
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.
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.