CISD2 downregulation participates in the ferroptosis process of human ovarian SKOV-3 cells through modulating the wild type p53-mediated GLS2/SAT1/SLC7A11 and Gpx4/TRF signaling pathway

作者全名："Wang, Yaqin; Yi, Yongfen"

作者地址："[Wang, Yaqin; Yi, Yongfen] Chongqing Med Univ, Sch Basic Med, Chongqing, Peoples R China; [Wang, Yaqin] North Sichuan Med Coll, Sch Basic Med, Nanchong, Peoples R China"

通信作者："Yi, YF (通讯作者)，Chongqing Med Univ, Sch Basic Med, Chongqing, Peoples R China."

来源：TISSUE & CELL

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001325362200001

JCR分区：Q2

影响因子：2.6

年份：2024

卷号：89

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：CISD2; Ferroptosis; p53; Apoptosis; Gpx4

摘要："CISD2 and ferroptosis participate in cancer development, but are rarely reported in ovarian cancer. This study aimed to clarify interaction between CISD2 and ferroptosis and evaluate related mechanisms. si-CISD2, wt-p53 and mut-p53 lentiviruses were transfected into SKOV-3 cells. CISD2 and p53 (wild/mutant p53) gene transcriptions were evaluated by RT-PCR. Cell viability, invasion ability, and migration capacity were determined. Expressions of ferroptosis-associated CISD2, p53, elastin, (3-catenin and levels of Gpx4 and TRF were examined. CISD2 downregulation (si-CISD2) has a significant inhibitory effect on cell activity and exerts a synergistic effect with p53. si-CISD2 and Wt-p53 markedly inhibited SKOV-3 invasion and migration capacity, compared to the downregulation control (si-NC) and overexpression control (ov-NC) group (p < 0.001). p53 expression was increased significantly in si-CISD2 treated SKOV-3, compared to si-NC treated cells (p < 0.05). si-CISD2 markedly decreased elastin and (3-catenin expression compared to the si-NC and ov-NC group (p < 0.001). si-CISD2 modulated ferroptosis-associated molecules (CDKN1A, GLS2, SAT1, SLC7A11), decreased Gpx4 and increased TRF levels in SKOV-3. si-CISD2 and Wt-p53 played an obvious synergistic role in regulating ferroptosisassociated molecules and Gpx4/TRF pathway molecules. In conclusion, CISD2 downregulation was involved in ferroptosis process of SKOV-3 cells. This effect of CISD2 was mediated by wild-type p53-associated GLS2/ SAT1/SLC7A11 and Gpx4/TRF pathway."

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