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생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis

  • Kaiyun Qin (Department of Gynecology, Hebei General Hospital) ;
  • Fenghua Zhang (Department of Breast & Thyroid Surgery, Hebei General Hospital) ;
  • Hongxia Wang (Department of Gynecology, Fourth Hospital of Hebei Medical University) ;
  • Na Wang (Department of Gynecology, Fourth Hospital of Hebei Medical University) ;
  • Hongbing Qiu (Department of Gynecology, Hebei Xingtai People's Hospital) ;
  • Xinzhuan Jia (Department of Reproductive Medicine, Fourth Hospital of Hebei Medical University) ;
  • Shan Gong (Department of Gynecology, Fourth Hospital of Hebei Medical University) ;
  • Zhengmao Zhang (Department of Gynecology, Fourth Hospital of Hebei Medical University)
  • 투고 : 2022.11.03
  • 심사 : 2023.01.04
  • 발행 : 2023.03.31
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초록

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.

키워드

과제정보

This study was supported by the Key Project of the Natural Science Foundation of Hebei Province (Grant No. H2020206223).

참고문헌

  1. Wu YH, Huang YF, Chen CC, Huang CY and Chou CY (2020) Comparing PI3K/Akt Inhibitors Used in Ovarian Cancer Treatment. Front Pharmacol 11, 206 
  2. Haddad G and Lorenzen JM (2019) Biogenesis and function of circular rnas in health and in disease. Front Pharmacol 10, 428 
  3. Yang X, Mei J, Wang H, Gu D, Ding J and Liu C (2020) The emerging roles of circular RNAs in ovarian cancer. Cancer Cell Int 20, 265 
  4. Shabaninejad Z, Vafadar A, Movahedpour A et al (2019) Circular RNAs in cancer: new insights into functions and implications in ovarian cancer. J Ovarian Res 12, 84 
  5. Conrad M and Pratt DA (2019) The chemical basis of ferroptosis. Nat Chem Biol 12, 1137-1147  https://doi.org/10.1038/s41589-019-0408-1
  6. Hadian K and Stockwell BR (2021) A roadmap to creating ferroptosis-based medicines. Nat Chem Biol 11, 1113-1116  https://doi.org/10.1038/s41589-021-00853-z
  7. Chen X, Li J, Kang R and Klionsky DJ (2021) Ferroptosis: machinery and regulation. Autophagy 17, 2054-2081  https://doi.org/10.1080/15548627.2020.1810918
  8. Zhou HH, Chen X, Cai LY et al (2019) Erastin reverses abcb1-mediated docetaxel resistance in ovarian cancer. Front Oncol 9, 1398 
  9. Zheng H, Shi L, Tong C, Liu Y and Hou M (2021) circSnx12 is involved in ferroptosis during heart failure by targeting miR-224-5p. Front Cardiovasc Med 8, 656093 
  10. Christian J and Thomas H (2001) Ovarian cancer chemotherapy. Cancer Treat Rev 27, 99-109  https://doi.org/10.1053/ctrv.2001.0219
  11. Xin C, Huang F, Wang J, Li J and Chen Q (2021) Roles of circRNAs in cancer chemoresistance (review). Oncol Rep 46, 225 
  12. Qu F, Wang L, Wang C, Yu L, Zhao K and Zhong H (2021) Circular RNA circ_0006168 enhances Taxol resistance in esophageal squamous cell carcinoma by regulating miR-194-5p/JMJD1C axis. Cancer Cell Int 21, 273 
  13. Wang M, Han D, Yuan Z et al (2018) Long non-coding RNA H19 confers 5-Fu resistance in colorectal cancer by promoting SIRT1-mediated autophagy. Cell Death Dis 9, 1149 
  14. Yu G, Zhou H, Yao W, Meng L and Lang B (2019) lncRNA TUG1 promotes cisplatin resistance by regulating CCND2 via epigenetically silencing mir-194-5p in bladder cancer. Mol Ther Nucleic Acids 16, 257-271  https://doi.org/10.1016/j.omtn.2019.02.017
  15. Xia M, Sheng L, Qu W et al (2021) MiR-194-5p enhances the sensitivity of nonsmall-cell lung cancer to doxorubicin through targeted inhibition of hypoxia-inducible factor-1. World J Surg Oncol 19, 174 
  16. An J, Lv W and Zhang Y (2017) LncRNA NEAT1 contributes to paclitaxel resistance of ovarian cancer cells by regulating ZEB1 expression via miR-194. Onco Targets Ther 10, 5377-5390  https://doi.org/10.2147/OTT.S147586
  17. Nakamura K, Sawada K, Miyamoto M et al (2019) Downregulation of miR-194-5p induces paclitaxel resistance in ovarian cancer cells by altering MDM2 expression. Oncotarget 10, 673-683  https://doi.org/10.18632/oncotarget.26586
  18. Hong T, Lei G, Chen X et al (2021) PARP inhibition promotes ferroptosis via repressing SLC7A11 and synergizes with ferroptosis inducers in BRCA-proficient ovarian cancer. Redox Biol 42, 101928