CircRAPGEF5 interacts with RBFOX2 to confer ferroptosis resistance by modulating alternative splicing of TFRC in endometrial cancer

Zhang, Jun; Chen, Shuaijun; Wei, Sitian; Cheng, Shuangshuang; Shi, Rui; Zhao, Rong; Zhang, Wei; Zhang, Qi; Hua, Teng; Feng, Da; Yu, Zhicheng; Wang, Hongbo

doi:10.1016/j.redox.2022.102493

Cited by 33 publications

(28 citation statements)

References 59 publications

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“…Ferroptosis is involved in a series of cancer processes, including diagnosis, prognosis, carcinogenesis, cancer resistance, and treatment of hepatocellular carcinoma (8)(9)(10), renal cell carcinoma (11)(12)(13), glioma (14)(15)(16), ovarian cancer (17)(18)(19), and so on. Furthermore, drugs such as quercetin, simvastatin and amentoflavone, as well as genes including CircRAPGEF5, protein tyrosine phosphatase non-receptor type 18 (PTPN18) and tyrosine kinase (ELK1) Oncogene participated in regulation of ferroptosis and thus played a role in EC (20)(21)(22)(23)(24)(25)(26). What's more, ferroptosis plays an important role in anti-tumor immunity.…”

Section: Introductionmentioning

confidence: 99%

Ferroptosis-related lncRNA model based on CFAP58-DT for predicting prognosis and immunocytes infiltration in endometrial cancer

Qin¹,

Qian²,

Cui³

et al. 2023

Ann Transl Med

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Background: Endometrial cancer (EC) is a kind of common gynecological tumor. Further study on the markers related to the prognosis of endometrial cancer is important for women worldwide. Methods:The Cancer Genome Atlas (TCGA) database was used to obtain the transcriptome profiling and clinical data. A model was built using packages based on R software. Immune-related databases were employed to analyze the infiltration of immunocytes. Quantitative real-time PCR (qRT-PCR), cell counting kit-8 (CCK-8), and transwell assays were utilized to investigate the role of CFAP58-DT in EC.Results: Following Cox regression analysis, 1,731 ferroptosis-related long non-coding RNA (lncRNA)were screened, and a 9-related lncRNA prognostic model was constructed. Patients were classified as highand low-risk according to their expression spectrum. Kaplan-Meier (KM) analysis showed that the prognosis of low-risk patients was poor. Operating characteristic curves, decision curve analysis, and a nomogram suggested the model could independently guide prognostic evaluation, with higher sensitivity, specificity, and efficiency than other common clinical characteristics. Gene Set Enrichment Analysis (GSEA) was conducted to determine the enriched pathways among the two groups and evaluation of the immune-infiltrating conditions were performed to help improve immune therapy. Finally, we conducted cytological studies on the model's most important indicators.Conclusions: Overall, we identified a prognostic ferroptosis-related lncRNA model based on CFAP58-DT for predicting the prognosis and immune-infiltrating conditions in EC. We concluded that the potential oncogenic role of CFAP58-DT can further guide immunotherapy and chemotherapy.

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Section: Introductionmentioning

confidence: 99%

Ferroptosis-related lncRNA model based on CFAP58-DT for predicting prognosis and immunocytes infiltration in endometrial cancer

Qin¹,

Qian²,

Cui³

et al. 2023

Ann Transl Med

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“…43 In endometrial cancer (EC), CircRAPGEF5 was shown to promote transferrin formation via exon 4 and to facilitate resistance to ferroptosis in EC cells through interaction with RNA-binding Fox-1 homolog 2 (RBFOX2). 44 These studies support continued comprehensive and in-depth exploration of circRNAs that influence ferroptosis as promising targets for therapeutic approaches for tumors of the reproductive system.…”

Section: Diseases Of the Reproductive Systemmentioning

confidence: 63%

“…Circ‐BGN, on the other hand, was shown to inhibit ferroptosis in HER2‐positive breast cancer cells by binding to OTU domain‐containing ubiquitin aldehyde‐binding protein 1 (OTUB1) and SLC7A11, and this regulation of ferroptosis was found to mediate trastuzumab resistance in HER2‐positive breast cancer 43 . In endometrial cancer (EC), CircRAPGEF5 was shown to promote transferrin formation via exon 4 and to facilitate resistance to ferroptosis in EC cells through interaction with RNA‐binding Fox‐1 homolog 2 (RBFOX2) 44 . These studies support continued comprehensive and in‐depth exploration of circRNAs that influence ferroptosis as promising targets for therapeutic approaches for tumors of the reproductive system.…”

Section: Circrnas Regulate Ferroptosis In Diseasementioning

confidence: 99%

CircRNA and ferroptosis in human disease: Insights for new treatments

Liu,

Zhou,

Cao

2023

Anim Models and Exp Med

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Circular RNA (circRNA), classified as a type of non‐coding RNA, has gained significant attention in the field of biology due to its distinctive ring structure and functional properties. Recent research has provided evidence that specific circRNAs have the ability to modulate disease progression through diverse mechanisms, one of which is by regulating cellular ferroptosis. Ferroptosis is a form of regulated cell death that is driven by iron dependency and lipid peroxidation, and extensive investigations have revealed a relationship between ferroptosis and disease development. In addition to evidence that both circRNAs and ferroptosis exert critical roles in disease progression, circRNAs have also been shown to actively mediate the process of ferroptosis. The relationship between circRNAs and ferroptosis therefore influences disease progression and offers novel targets for disease treatment. By directly or indirectly modulating the expression of circRNAs that regulate the expression of ferroptosis‐related proteins, it may be possible to impact disease progression by promoting or inhibiting ferroptosis. Current research indicates such approaches may hold significant value in a wide variety of common diseases across physiological systems. This review comprehensively summarizes the findings of recent studies investigating the roles of circRNAs in the regulation of ferroptosis in various diseases.

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“…LncRNA BBOX1‐AS1 is highly expressed in esophageal squamous cell cancer (ESCC) tissues, whereas knockdown of BBOX1‐AS1 inhibited SLC7A11 expression by up‐regulating miR‐513a‐3p, thereby promoting ferroptosis and suppressing the proliferation of ESCC cells (Pan et al, 2022). CircRAPGEF5 interacted with RNA‐binding fox‐1 homolog 2 (RBFOX2) to block the binding of RBFOX2 to the pre‐mRNA of TFR1 in the nucleus and thus generated TFR1 with exon‐4 skipping (J. Zhang, Chen, et al, 2022). Owing to the lack of iron transport activity of this splicing variant, endometrial cancer (EC) cells exhibited reduced iron levels and ferroptosis resistance.…”

Section: Multifaceted Roles Of Ferroptosis In Cancermentioning

confidence: 99%

Ferroptosis: Potential opportunities for natural products in cancer therapy

Nie,

Shen,

Zhou

et al. 2023

Phytotherapy Research

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Cancer cells often exhibit defects in the execution of cell death, resulting in poor clinical outcomes for patients with many cancer types. Ferroptosis is a newly discovered form of programmed cell death characterized by intracellular iron overload and lipid peroxidation in the cell membrane. Increasing evidence suggests that ferroptosis is closely associated with a wide variety of physiological and pathological processes, particularly in cancer. Notably, various bioactive natural products have been shown to induce the initiation and execution of ferroptosis in cancer cells, thereby exerting anticancer effects. In this review, we summarize the core regulatory mechanisms of ferroptosis and the multifaceted roles of ferroptosis in cancer. Importantly, we focus on natural products that regulate ferroptosis in cancer cells, such as terpenoids, polyphenols, alkaloids, steroids, quinones, and polysaccharides. The clinical efficacy, adverse effects, and drug–drug interactions of these natural products need to be evaluated in further high‐quality studies to accelerate their application in cancer treatment.

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CircRAPGEF5 interacts with RBFOX2 to confer ferroptosis resistance by modulating alternative splicing of TFRC in endometrial cancer

Cited by 33 publications

References 59 publications

Ferroptosis-related lncRNA model based on CFAP58-DT for predicting prognosis and immunocytes infiltration in endometrial cancer

Ferroptosis-related lncRNA model based on CFAP58-DT for predicting prognosis and immunocytes infiltration in endometrial cancer

CircRNA and ferroptosis in human disease: Insights for new treatments

Ferroptosis: Potential opportunities for natural products in cancer therapy

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