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Molecular mechanism of cell ferroptosis and research progress in regulation of ferroptosis by noncoding RNAs in tumor cells.

ABSTRACT: Ferroptosis is a newly identified form of nonapoptotic regulated cell death characterized by iron-dependent accumulation of lipid reactive oxygen species. Morphologically and biochemically different from known types of cell death and apoptosis, ferroptosis promotes nervous system diseases, renal failure, ischemia-reperfusion injury, and the treatment of tumors. It could be induced by several mechanisms, including inhibition of glutathione peroxidase 4, lack of cysteine, and peroxidation of polyunsaturated fatty acids, but could be inhibited by iron chelators, lipophilic antioxidants, and some specific inhibitors. Ferroptosis is found to be closely related to the tumorigenesis, invasion, and metastasis of tumors. Noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), microRNAs, and circular RNAs, do not encode proteins. NcRNAs are found to be capable of regulating the molecular mechanism of ferroptosis in tumor cells post transcription. Ferroptosis provides a new method for cancer treatment. Although several studies have confirmed the important role of ferroptosis in cancer treatment, its specific affecting mechanism is unclear. Here we reviewed the molecular mechanism of ferroptosis in tumor cells and the relationship between ferroptosis and the three important ncRNAs.

SUBMITTER: Xie B

PROVIDER: S-EPMC8115351 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Ovarian cancer (OC) is a highly malignant gynecologic tumor with few treatments available and poor prognosis with the currently available diagnostic markers and interventions. More effective methods for diagnosis and treatment are urgently needed. Although the current evidence implicates ferroptosis in the development and therapeutic responses of various types of tumors, it is unclear to what extent ferroptosis affects OC. To explore the potential of ferroptosis-related genes as biomarkers and molecular targets for OC diagnosis and intervention, this study collected several datasets from The Cancer Genome Atlas-OC (TCGA-OC), analyzed and identified the coexpression profiles of 60 ferroptosis-related genes and two subtypes of OC with respect to ferroptosis and further examined and analyzed the differentially expressed genes between the two subtypes. The results indicated that the expression levels of ferroptosis genes were significantly correlated with prognosis in patients with OC. Single-factor Cox and LASSO analysis identified eight lncRNAs from the screened ferroptosis-related genes, including lncRNAs RP11-443B7.3, RP5-1028K7.2, TRAM2-AS1, AC073283.4, RP11-486G15.2, RP11-95H3.1, RP11-958F21.1, and AC006129.1. A risk scoring model was constructed from the ferroptosis-related lncRNAs and showed good performance in the evaluation of OC patient prognosis. The high- and low-risk groups based on tumor scores presented obvious differences in clinical characteristics, tumor mutation burden, and tumor immune cell infiltration, indicating that the risk score has a good ability to predict the benefit of immunotherapy and may provide data to support the implementation of precise immunotherapy for OC. Although in vivo tests and research are needed in the future, our bioinformatics analysis powerfully supported the effectiveness of the risk signature of ferroptosis-related lncRNAs for prognosis prediction in OC. The findings suggest that these eight identified lncRNAs have great potential for development as diagnostic markers and intervention targets for OC and that patients with high ferroptosis-related lncRNA expression will receive greater benefits from conventional chemotherapy or treatment with ferroptosis inducers.

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Molecular mechanism of cell ferroptosis and research progress in regulation of ferroptosis by noncoding RNAs in tumor cells.

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