circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis
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초록
Ovarian cancer (OC) is the most common gynecological malignancyworldwide, and chemoresistance occurs in most patients,resulting in treatment failure. A better understanding of themolecular processes underlying drug resistance is crucial fordevelopment of efficient therapies to improve OC patient outcomes. Circular RNAs (circRNAs) and ferroptosis play crucialroles in tumorigenesis and resistance to chemotherapy. However,little is known about the role(s) of circRNAs in regulatingferroptosis in OC. To gain insights into cisplatin resistance inOC, we studied the ferroptosis-associated circRNA circSnx12. We evaluated circSnx12 expression in OC cell lines and tissuesthat were susceptible or resistant to cisplatin using quantitativereal-time PCR. We also conducted in vitro and in vivoassays examining the function and mechanism of lnc-LBCSs. Knockdown of circSnx12 rendered cisplatin-resistant OC cellsmore sensitive to cisplatin in vitro and in vivo by activatingferroptosis, which was at least partially abolished by downregulationof miR-194-5p. Molecular mechanics studies indicatethat circSnx12 can be a molecular sponge of miR-194-5p, whichtargets SLC7A11. According to our findings, circSnx12 amelioratescisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effectivetherapeutic target for overcoming cisplatin resistance in OC.
Abstract
Ovarian cancer (OC) is the most common gynecological malignancyworldwide, and chemoresistance occurs in most patients,resulting in treatment failure. A better understanding of themolecular processes underlying drug resistance is crucial fordevelopment of efficient therapies to improve OC patient outcomes. Circular RNAs (circRNAs) and ferroptosis play crucialroles in tumorigenesis and resistance to chemotherapy. However,little is known about the role(s) of circRNAs in regulatingferroptosis in OC. To gain insights into cisplatin resistance inOC, we studied the ferroptosis-associated circRNA circSnx12. We evaluated circSnx12 expression in OC cell lines and tissuesthat were susceptible or resistant to cisplatin using quantitativereal-time PCR. We also conducted in vitro and in vivoassays examining the function and mechanism of lnc-LBCSs. Knockdown of circSnx12 rendered cisplatin-resistant OC cellsmore sensitive to cisplatin in vitro and in vivo by activatingferroptosis, which was at least partially abolished by downregulationof miR-194-5p. Molecular mechanics studies indicatethat circSnx12 can be a molecular sponge of miR-194-5p, whichtargets SLC7A11. According to our findings, circSnx12 amelioratescisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effectivetherapeutic target for overcoming cisplatin resistance in OC.
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