Ferroptosis in Ovarian Cancer: A Novel Therapeutic Strategy

Li, Lanyu; Qiu, Cheng; Hou, Min; Wang, Xinyu; Huang, Changzhen; Zou, Jialin; Liu, Tianyi; Qu, Jingyao

doi:10.3389/fonc.2021.665945

Cited by 47 publications

(34 citation statements)

References 66 publications

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“…Moreover, the function of OGN in OC progression is closely related to m6A modification and ferroptosis. Ferroptosis is a novel recognized type of cell death induced by iron accumulation, lipid peroxidation and glutathione deprivation, indicating a connection with a variety of disorders and suggesting great potential in OC therapy [ 57 ]. The ectopic expression of m6A methylation regulators is involved in OC progression.…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes associated with polycystic ovary syndrome (PCOS) and ovarian cancer using an integrated bioinformatics analysis

Zou

Liao

et al. 2022

J Ovarian Res

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Background Accumulating evidence suggests a strong association between polycystic ovary syndrome (PCOS) and ovarian cancer (OC), but the potential molecular mechanism remains unclear. In this study, we identified previously unrecognized genes that are significantly correlated with PCOS and OC via bioinformatics. Materials and methods Multiple bioinformatic analyses, such as differential expression analysis, univariate Cox analysis, functional and pathway enrichment analysis, protein–protein interaction (PPI) network construction, survival analysis, and immune infiltration analysis, were utilized. We further evaluated the effect of OGN on FSHR expression via immunofluorescence. Results TCGA-OC, GSE140082 (for OC) and GSE34526 (for PCOS) datasets were downloaded. Twelve genes, including RNF144B, LPAR3, CRISPLD2, JCHAIN, OR7E14P, IL27RA, PTPRD, STAT1, NR4A1, OGN, GALNT6 and CXCL11, were identified as signature genes. Drug sensitivity analysis showed that OGN might represent a hub gene in the progression of PCOS and OC. Experimental analysis found that OGN could increase FSHR expression, indicating that OGN could regulate the hormonal response in PCOS and OC. Furthermore, correlation analysis indicated that OGN function might be closely related to m6A and ferroptosis. Conclusions Our study identified a 12-gene signature that might be involved in the prognostic significance of OC. Furthermore, the hub gene OGN represent a significant gene involved in OC and PCOS progression by regulating the hormonal response.

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Section: Discussionmentioning

confidence: 99%

Identification of key genes associated with polycystic ovary syndrome (PCOS) and ovarian cancer using an integrated bioinformatics analysis

Zou

Liao

et al. 2022

J Ovarian Res

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“…These results further confirm the significance of miR-27-3p. In addition to TNBC, Olaparib was also approved for the treatment of ovarian cancer ( 58 , 59 ). For this reason, the expression levels of miR-27-3p and PSEN-1 in ovarian cancer tissue samples will be further tested in the future, and whether miR-27-3p can upregulate ovarian cancer cells’ sensitivity to Olparib.…”

Section: Discussionmentioning

confidence: 99%

miR-27-3p Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to the Antitumor Agent Olaparib by Targeting PSEN-1, the Catalytic Subunit of Γ-Secretase

et al. 2021

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Olaparib has been used in the treatment of triple-negative breast cancer (TNBC) with BRCA mutations. In the present study, we demonstrated the effect of miR-27-3p on the γ-secretase pathway by regulating the sensitivity of TNBC cells to olaparib. miR-27-3p, a microRNA with the potential to target PSEN-1, the catalytic subunit of γ-secretase mediating the second step of the cleavage of the Notch protein, was identified by the online tool miRDB and found to inhibit the expression of PSEN-1 by directly targeting the 3’-untranslated region (3’-UTR) of PSEN-1. The overexpression of miR-27-3p inhibited the activation of the Notch pathway via the inhibition of the cleavage of the Notch protein, mediated by γ-secretase, and, in turn, enhanced the sensitivity of TNBC cells to the antitumor agent olaparib. Transfection with PSEN-1 containing mutated targeting sites for miR-27-3p or the expression vector of the Notch protein intracellular domain (NICD) almost completely blocked the effect of miR-27-3p on the Notch pathway or the sensitivity of TNBC cells to olaparib, respectively. Therefore, our results suggest that the miR-27-3p/γ-secretase axis participates in the regulation of TNBC and that the overexpression of miR-27-3p represents a potential approach to enhancing the sensitivity of TNBC to olaparib.

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“…Ferroptosis has been extensively studied in various disorders and exhibits great potential in antitumor therapy ( 12 , 56 ). Tumor diseases marked by angiogenesis, which accounts for metastasis and poor prognosis, are in most cases treated with surgical resection, radiotherapy, or combined chemotherapy ( 57 ). Herein, the evocation of ferroptosis could be regarded as a new approach to halt osteosarcoma growth and could provide support for the treatment of difficult tumors ( 20 , 58 ).…”

Section: Hopeful Investment In Osteosarcomamentioning

confidence: 99%

Novel Therapeutic Savior for Osteosarcoma: The Endorsement of Ferroptosis

et al. 2022

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Ferroptosis has recently been discovered as an iron-dependent and non-apoptotic regulated mechanism of cell death. The induction of ferroptosis in tumor cells improves tumor treatment, making it a current research hotspot. Mechanistically, it starts by lipid peroxidation, iron accumulation, reactive oxygen species (ROS) production, and glutathione deprivation, highlighting novel treatment opportunities for many tumors and neurodegenerative disorders. Several tumor cell lines are resistant to ferroptosis inducers, even when the ferroptosis key enzyme glutathione peroxidase 4 (GPX4) is blocked, indicating that other important elements are also involved in this process. Ferroptosis-suppressor-protein 1 (FSP1) was discovered to be one of these elements in addition to a few others such as ferroptotic gatekeepers like GTP cyclohydrolase 1 (GCH1) and dihydroorotate dehydrogenase (DHODH). Osteosarcoma is the most common primary malignant bone tumor observed most frequently in children and adolescents. Several studies demonstrated that ferroptosis plays a critical role in the treatment of osteosarcoma, in particular drug-resistant osteosarcoma cells. We outlined four primary regulators involved in ferroptosis in this article, reviewed previously published studies of ferroptosis in osteosarcoma to provide covert insights about osteosarcoma treatment, and highlighted several critical issues to point out future research possibilities.

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Ferroptosis in Ovarian Cancer: A Novel Therapeutic Strategy

Cited by 47 publications

References 66 publications

Identification of key genes associated with polycystic ovary syndrome (PCOS) and ovarian cancer using an integrated bioinformatics analysis

Identification of key genes associated with polycystic ovary syndrome (PCOS) and ovarian cancer using an integrated bioinformatics analysis

miR-27-3p Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to the Antitumor Agent Olaparib by Targeting PSEN-1, the Catalytic Subunit of Γ-Secretase

Novel Therapeutic Savior for Osteosarcoma: The Endorsement of Ferroptosis

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