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. 2023 Mar;56(2):184-189.
doi: 10.5483/BMBRep.2022-0175.

circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis

Kaiyun Qin  1 , Fenghua Zhang  2 , Hongxia Wang  3 , Na Wang  3 , Hongbing Qiu  4 , Xinzhuan Jia  5 , Shan Gong  3 , Zhengmao Zhang  3
Affiliations

circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis (V体育官网入口)

Kaiyun Qin et al. BMB Rep. 2023 Mar.

Erratum in

Abstract

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 VSports手机版. 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. [BMB Reports 2023; 56(3): 184-189]. .

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Conflict of interest statement (VSports最新版本)

CONFLICTS OF INTEREST

The authors have no conflicting interests.

Figures

Fig. 1
Fig. 1
Assessment of the role of ferroptosis and CircSnx12 expression during DDP-induced chemoresistance in ovarian cancer. (A, B) Cell viability was detected in SKOV3 and A2780 cells treated with Erastin, DFO, or Fer-1 after treatment with DDP. Fe2+ was detected by staining with FerroOrange probe (C) and measured using an ELISA kit (D) in DDP-treated SKOV3, A2780, SKOV3/DDP, and A2780/DDP cells. Scale bars, 50 μm. (E) Ferroptosis protein biomarkers SLC7A11, GPX4, and 4-HNE were examined by Western blotting. (F) Quantitative real-time PCR (qRT-PCR) quantification of circSnx12 expression in OC tissues susceptible or resistant to DDP. (G) Fluorescence in situ hybridization (FISH) results examining circSnx12 distribution in OC tissues sensitive or resistant to DDP. Scale bars, 200 μm. (H) CircSnx12 expression was elevated in DDP-resistant A2780/DDP and SKOV3/DDP cells relative to parental cells. Significance: ***P < 0.001.
Fig. 2
Fig. 2
Knockdown of circSnx12 increased DDP and ferroptosis sensitivity in resistant ovarian cancer. (A) The influence of shRNA targeting circSnx12 was evaluated by quantitative real-time PCR (qRT-PCR) in A2780/DDP and SKOV3/DDP cells. (B) DDP sensitivity was examined using a CCK-8 assay. (C) The percentage of EdU-stained cells was substantially reduced by circSnx12 knockdown in A2780/DDP and SKOV3/DDP cells. Scale bars, 100 μm. (D) Flow cytometric analysis and quantification of cell apoptosis following DDP administration in A2780/DDP and SKOV3/DDP cells transfected with shRNA-circSnx12 or shRNA-control. (E) A GSH Assay kit was used to examine intracellular levels of the antioxidant thiol GSH following DDP treatment in A2780/DDP and SKOV3/DDP cells transfected with shRNA-circSnx12 or shRNA-control. (F) Lipid peroxidation was detected using flow cytometry in A2780/DDP and SKOV3/DDP cells following DDP treatment. Fe2+ was detected with FerroOrange probe staining (G) and measured using an ELISA kit (H) in A2780/DDP and SKOV3/DDP cells following DDP treatment. Scale bar, 50 μm. (I) Ferroptosis protein biomarkers SLC7A11, GPX4, and 4-HNE were examined using western blotting. (J) A mouse xenograft tumor model was used to examine whether circSnx12 knockdown contributed to the antitumor effects of DDP. (K) Immunohistochemical image demonstrating expression of Ki-67 and ferroptosis product 4-HNE in xenograft tumors. Scale bar, 50 μm. Significance: *** P < 0.001.
Fig. 3
Fig. 3
CircSnx12 functions as a sponge toward miR-194-5p to mediate DDP and ferroptosis sensitivity in DDP-treated resistant ovarian cancer. (A) The predicted binding domains between circSnx12 and miR-195-5p are presented. (B) miR-194-5p expression in OC tissues sensitive or resistant to DDP was quantified by qRT-PCR. (C) Correlation analysis of circSnx12 and miR-195-5p expression in OC is shown. (D) circSnx12 and miR-195-5p localization as detected by FISH assay in SKOV3/DDP cells. (E) CircSnx12 is shown to be a direct target of miR-195-5p utilizing a dual-luciferase reporter assay. (F) qRT-PCR analysis of miR-195-5p expression in SKOV3/DDP cells in different groups. (G) miR-194-5p mRNA levels were determined utilizing qRT-PCR in DDP-treated A2780/DDP and SKOV3/DDP cells transfected with shRNA-circSnx12, miR-194-5p-inhibitor or respective controls. (H) Cell proliferation was monitored through EdU assay. (I) A2780/DDP and SKOV3/DDP cells were transfected with shRNA-circSnx12, miR-194-5p-inhibitor, or respective controls, and the apoptosis rate, and the proportion of cell apoptosis caused by DDP administration, were measured by flow cytometry analysis. (J) Lipid peroxidation was detected with flow cytometry in A2780/DDP and SKOV3/DDP cells transfected with shRNA-circSnx12, miR-194-5p-inhibitor, or respective controls after treatment with DDP. (K) Fe2+ was detected using an ELISA kit. (L) Ferroptosis protein biomarkers SLC7A11, GPX4, and 4-HNE were evaluated by Western blotting. Significance: *P < 0.05, **P < 0.01, ***P < 0.001.
Fig. 4
Fig. 4
SLC7A11 is a direct target of miR-194-5p in ovarian cancer. (A) Targetscan was employed to predict binding domains between miR-194-5p and SLC7A11. The interplay between miR-194-5p and SLC7A11 in A2780/DDP and SKOV3/DDP cells was verified by luciferase reporter assay. (B) IHC analysis of SLC7A11 expression level in DDP-resistant/sensitive ovarian tumor tissues. Scale bar, 200 μm. (C) SLC7A11 protein was monitored by immunofluorescence in OC cells and parental cells that are DDP-resistant. Scale bar, 20 μm. (D, E) The impacts of miR-194-5p on SLC7A11 expression in A2780/DDP and SKOV3/DDP cells were examined by qPCR and western blot. (F) The percentage of EdU-stained cells was significantly rescued by SLC7A11 overexpression in A2780/DDP and SKOV3/DDP cells. (G) Flow cytometric analysis and quantification of cell apoptosis after DDP administration in A2780/DDP and SKOV3/DDP cells correspondingly transfected. Significance: **P < 0.01, ***P < 0.001.
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References

    1. Wu YH, Huang YF, Chen CC, Huang CY, Chou CY. Comparing PI3K/Akt Inhibitors Used in Ovarian Cancer Treatment. Front Pharmacol. 2020;11:206. doi: 10.3389/fphar.2020.00206.01566e0f30034ecaa16f6d23dd4b78a3 - DOI (VSports在线直播) - PMC - PubMed
    1. Haddad G, Lorenzen JM. Biogenesis and function of circular rnas in health and in disease. Front Pharmacol. 2019;10:428. doi: 10.3389/fphar.2019.00428.844fae42894645ce9cc7589e960c3769 - DOI - PMC - PubMed
    1. Yang X, Mei J, Wang H, Gu D, Ding J, Liu C. The emerging roles of circular RNAs in ovarian cancer. Cancer Cell Int. 2020;20:265. doi: 10.1186/s12935-020-01367-9.25336bec5c5440a1a8ddd32ce58c6b4e - DOI - PMC - PubMed
    1. Shabaninejad Z, Vafadar A, Movahedpour A, et al. Circular RNAs in cancer: new insights into functions and implications in ovarian cancer. J Ovarian Res. 2019;12:84. doi: 10.1186/s13048-019-0558-5.74d7c58e2753451cbcd089139535bf05 - DOI - PMC - PubMed
    1. Conrad M, Pratt DA. The chemical basis of ferroptosis. Nat Chem Biol. 2019;12:1137–1147. doi: 10.1038/s41589-019-0408-1. - DOI - PubMed

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