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circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis
Kaiyun Qin1,# (physician), Fenghua Zhang2,# (physician), Hongxia Wang3 (Research worker), Na Wang3 (Research worker), Hongbing Qiu3 (Research worker), Xinzhuan Jia5 (physician), Shan Gong3 (Research worker), Zhengmao Zhang 3,* (physician in charge)
1Department of Gynecology and 2Department of Breast & Thyroid Surgery, Hebei General Hospital,
3Department of Gynecology, Fourth Hospital of Hebei Medical University,
4Department of Gynecology, Hebei Xingtai People’s Hospital,
5Department of Reproductive medicine, Fourth Hospital of Hebei Medical University
Ovarian cancer (OC) is the most common gynecological malignancy worldwide, and chemoresistance occurs in most patients, resulting in treatment failure. A better understanding of the molecular processes underlying drug resistance is crucial for development of efficient therapies to improve OC patient outcomes. Circular RNAs (circRNAs) and ferroptosis play crucial roles in tumorigenesis and resistance to chemotherapy. However, little is known about the role(s) of circRNAs in regulating ferroptosis in OC. To gain insights into cisplatin resistance in OC, we studied the ferroptosis-associated circRNA circSnx12. We evaluated circSnx12 expression in OC cell lines and tissues that were susceptible or resistant to cisplatin using quantitative real-time PCR. We also conducted in vitro and in vivo assays examining the function and mechanism of lnc-LBCSs. Knockdown of circSnx12 rendered cisplatin-resistant OC cells more sensitive to cisplatin in vitro and in vivo by activating ferroptosis, which was at least partially abolished by downregulation of miR-194-5p. Molecular mechanics studies indicate that circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/ SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in OC.
Abstract, Accepted Manuscript(in press) [Submitted on November 3, 2022, Accepted on January 4, 2023]
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