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Ubiquitination, a crucial post-translational modification, plays a vital role in cancer progression. The present research focused on the function of ubiquitin-specific protease 13 (USP13) and its potential mechanism related to leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) in cisplatin (DDP) resistance and ferroptosis of ovarian cancer (OC).

Real-time quantitative PCR and Western blotting were used for mRNA and protein detection. The half-maximal inhibitory concentration (IC50) of DDP was determined using CCK-8 assay. Cell proliferation, apoptosis, and migration were assessed through colony formation/EdU assays, flow cytometry, and transwell/wound healing assays, respectively. Ferroptosis was analyzed by detecting reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), Fe

2+

level and protein marker expression. Co-immunoprecipitation (Co-IP) assay was applied for protein interaction and ubiquitination analysis. Xenograft studies were constructed for in vivo research.

LGR4 expression was increased in DDP-resistant OC tissues and cell lines. After LGR4 was downregulated, chemoresistance and malignant characteristics such as proliferation and migration were suppressed while ferroptosis was promoted in DDP-resistant OC cells. USP13 served as a deubiquitinating enzyme to enhance LGR4 protein stability. USP13 inhibition attenuated DDP resistance and promoted ferroptosis by targeting LGR4. LGR4 knockdown could enhance chemosensitivity of tumor tissues to DDP in mice.These findings elucidated that USP13 stabilized LGR4 protein to regulate DDP resistance and ferroptosis in OC. Targeting the USP13/LGR4 axis represents a potential therapeutic strategy to overcome DDP resistance in OC.

LGR4 inhibition reduces chemoresistance and promotes ferroptosis in cisplatin-resistant ovarian cancer cells.

USP13 stabilizes LGR4 protein by deubiquitination.

LGR4 can reverse the effects of USP13 knockdown on cisplatin resistance and ferroptosis

LGR4 inhibition reduces chemoresistance and promotes ferroptosis in cisplatin-resistant ovarian cancer cells.USP13 stabilizes LGR4 protein by deubiquitination.LGR4 can reverse the effects of USP13 knockdown on cisplatin resistance and ferroptosis

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참고문헌 (30건) : 자료제공( 네이버학술정보 )

참고문헌 목록에 대한 테이블로 번호, 참고문헌, 국회도서관 소장유무로 구성되어 있습니다.
번호 참고문헌 국회도서관 소장유무
1 Molecular Biomarkers for the Early Detection of Ovarian Cancer 미소장
2 Ovarian cancer 미소장
3 Therapeutic strategies to overcome cisplatin resistance in ovarian cancer 미소장
4 Ferroptosis and Cancer: Mitochondria Meet the “Iron Maiden” Cell Death 미소장
5 Ferroptosis in cancer therapy: a novel approach to reversing drug resistance 미소장
6 Targeting ferroptosis in ovarian cancer: Novel strategies to overcome chemotherapy resistance 미소장
7 The role of ubiquitination and deubiquitination in tumor invasion and metastasis 미소장
8 E3 ligases and deubiquitinating enzymes regulating the MAPK signaling pathway in cancers 미소장
9 USP13: A therapeutic target for combating tumorigenesis and antitumor therapy resistance 미소장
10 Deubiquitinase USP13 dictates MCL1 stability and sensitivity to BH3 mimetic inhibitors 미소장
11 USP13 regulates the RAP80-BRCA1 complex dependent DNA damage response 미소장
12 The Role of LGR4 (GPR48) in Normal and Cancer Processes 미소장
13 LGR4 overexpression is associated with clinical parameters and poor prognosis of serous ovarian cancer 미소장
14 LGR4 maintains HGSOC cell epithelial phenotype and stem-like traits 미소장
15 International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis 미소장
16 LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells 미소장
17 Effect of LGR4/EGFR signaling on cell growth and cancer stem cell-like characteristics in liver cancer 미소장
18 DSPP-MMP20 gene silencing downregulates cancer stem cell markers in human oral cancer cells 미소장
19 Induction of ferroptosis by ATF3 elevation alleviates cisplatin resistance in gastric cancer by restraining Nrf2/Keap1/xCT signaling 미소장
20 HMGA1 drives chemoresistance in esophageal squamous cell carcinoma by suppressing ferroptosis 미소장
21 Shikonin and cisplatin synergistically overcome cisplatin resistance of ovarian cancer by inducing ferroptosis via upregulation of HMOX1 to promote Fe2+ accumulation 미소장
22 Ferroptosis: machinery and regulation 미소장
23 Deubiquitylase YOD1 regulates CDK1 stability and drives triple-negative breast cancer tumorigenesis 미소장
24 GSK3β and UCHL3 govern RIPK4 homeostasis via deubiquitination to enhance tumor metastasis in ovarian cancer 미소장
25 USP13 promotes deubiquitination of ZHX2 and tumorigenesis in kidney cancer 미소장
26 USP13 deubiquitinates and stabilizes cyclin D1 to promote gastric cancer cell cycle progression and cell proliferation 미소장
27 N6-methyladenosine-modified USP13 induces pro-survival autophagy and imatinib resistance via regulating the stabilization of autophagy-related protein 5 in gastrointestinal stromal tumors 미소장
28 USP13 regulates ferroptosis in chicken follicle granulosa cells by deubiquitinating ATG7 미소장
29 USP13 facilitates a ferroptosis-to-autophagy switch by activation of the NFE2L2/NRF2-SQSTM1/p62-KEAP1 axis dependent on the KRAS signaling pathway 미소장
30 GPCR48/LGR4 promotes tumorigenesis of prostate cancer via PI3K/Akt signaling pathway 미소장

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