Targeting ferroptosis in osteosarcoma

Zhao, Jiazheng; Zhao, Yi; Ma, Xiaowei; Zhang, Benzheng; Feng, Helin

doi:10.1016/j.jbo.2021.100380

Cited by 27 publications

(33 citation statements)

References 87 publications

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“…We have previously reported that ferroptosis can impact chemotherapy resistance in patients with OS 13 . Chemotherapy, a common management for cancer, provides varying degrees of therapeutic efficacy for most human cancers 22 .…”

Section: Discussionmentioning

confidence: 99%

“…Distinct from apoptosis, ferroptosis, as a nontraditional RCD form featured by iron-dependent accumulation of lipid reactive oxygen species 11 , has been revealed to function as a pivotal role in tumor chemoresistance 12 . In particular, for OS, we identified through previous studies that ferroptosis may be tightly correlated with OS chemoresistance 13 . Ferroptosis is considered to be of great potential in antagonizing chemoresistance for OS 14 , however, further studies on the mechanisms associated with the action of ferroptosis on OS chemoresistance and the essential molecules involved are extremely rare.…”

Section: Introductionmentioning

confidence: 99%

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Outstanding prognostic value of novel ferroptosis-related genes in chemoresistance osteosarcoma patients

Zhao

et al. 2022

Sci Rep

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Osteosarcoma (OS) is the most common bone-derived tumor, and chemoresistance is a pivotal factor in the poor prognosis of patients with OS. Ferroptosis, as an emerging modality of regulated cell death, has demonstrated potential value in tumor chemoresistance studies. Through the gene expression omnibus database in conjunction with the FerrDb database, we identified novel ferroptosis-related differentially expressed genes (DEGs) involving chemoresistance in OS patients. Subsequently, enrichment analysis, protein–protein interaction network analysis and survival analysis were performed sequentially to recognize the hub genes and ultimately to construct a predictive model. The model constructed from the TARGET database was exhibited in a nomogram and assessed by calibration curves. The prognostic value of the model and hub genes was validated separately by an independent cohort. Twenty-two ferroptosis-related DEGs were identified, including 16 up-regulated and 6 down-regulated. Among them, expressions of CBS, COCS1, EGFR, as hub genes, were significantly associated with the prognosis of OS patients and were evidenced as independent prognostic factors. An efficient prognostic model covering hub gene expressions and clinical variables was developed and validated. Combining the results of hub genes in differential analysis, the actions of hub genes in ferroptosis, and the prognostic relevance of hub genes in patients, we revealed that CBS, SOCS1 and EGFR might play essential roles in OS and its chemoresistance with potential research and clinical value.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Outstanding prognostic value of novel ferroptosis-related genes in chemoresistance osteosarcoma patients

Zhao

et al. 2022

Sci Rep

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“…Osteosarcoma (OS) is the most frequent bone tumour in children and adolescents, in addition to being the most common aggressive malignancy originating from mesenchymal cells [ 1 , 2 ]. Although neoadjuvant chemotherapy combined with surgery and postoperative chemotherapy has been used to treat OS, the five-year survival rate of OS is not satisfactory on account of development of early metastases and chemotherapy resistance [ 3 , 4 ]. Thus, it is imperative to find new targets and pharmaceuticals to improve the prognosis.…”

Section: Introductionmentioning

confidence: 99%

Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

Luo

Gao

Zou

et al. 2021

Oxidative Medicine and Cellular Longevity

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Ferroptosis is a new form of regulated cell death, which is mediated by intracellular iron. Although it is reported that bavachin has antitumour effects on several tumour cells and prompts the reactive oxygen species (ROS) generation, it is unclear whether ferroptosis can be induced by bavachin in osteosarcoma (OS) cells. In this study, we found that bavachin inhibits the viability of MG63 and HOS OS cell lines along with an increase in the ferrous iron level, ROS accumulation, malondialdehyde overexpression, and glutathione depletion. Moreover, iron chelators (deferoxamine), antioxidants (Vit E), and ferroptosis inhibitors (ferrostatin-1 and liproxstatin-1) reverse bavachin-induced cell death. Bavachin also altered the mitochondrial morphology of OS cells, leading to smaller mitochondria, higher density of the mitochondrial membrane, and reduced mitochondrial cristae. Further investigation showed that bavachin upregulated the expression of transferrin receptor, divalent metal transporter-1, and P53, along with downregulating the expression of ferritin light chain, ferritin heavy chain, p-STAT3 (705), SLC7A11, and glutathione peroxidase-4 in OS cells. More importantly, STAT3 overexpression, SLC7A11 overexpression, and pretreatment with pifithrin-α (P53 inhibitor) rescued OS cell ferroptosis induced by bavachin. The results show that bavachin induces ferroptosis via the STAT3/P53/SLC7A11 axis in OS cells.

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“…Most current therapeutic regimens work by inducing apoptosis in tumor cells, and once tumor cells undergo apoptotic escape, they become resistant to drugs, leading to reduced treatment sensitivity. As research progresses, the implications of ferroptosis in the development, progression, and multi-drug resistance of osteosarcoma are becoming better known, providing new avenues for treating osteosarcoma and overcoming chemoresistance (74). For illustration, it was found that MicroRNA-1287-5p promotes ferroptosis in osteosarcoma cells by inhibiting GPX4, but its expression is downregulated in human osteosarcoma relative to controls (78).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of a Ferroptosis-Related lncRNA Signature for Predicting Prognosis and Immune Landscape in Osteosarcoma

Zhang

Liu

et al. 2022

Front. Oncol.

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Research on the implications of ferroptosis in tumors has increased rapidly in the last decades. There are evidences that ferroptosis is involved in several aspects of cancer biology, including tumor progression, metastasis, immunomodulation, and therapeutic response. Nonetheless, the interaction between ferroptosis-related lncRNAs (FRLs) and the osteosarcoma immune microenvironment is poorly understood. In this study, a risk model composed of FRLs was developed using univariate and LASSO Cox regression analyses. On the basis of this model, FRL scores were calculated to systematically explore the role of the model in predicting the prognosis and immune characteristics of osteosarcoma patients. Survival analysis showed that osteosarcoma samples with lower FRL-score had better overall survival. After predicting the abundance of immune cells in osteosarcoma microenvironment by single-sample gene-set enrichment analysis (ssGSEA) and ESTIMATE analysis, we found that the FRL-score could distinguish immune function, immune score, stromal score, tumor purity, and tumor infiltration of immune cells in different osteosarcoma patients. In addition, FRL-score was also associated with immune checkpoint gene expression and half-maximal inhibitory concentration of chemotherapeutic agents. Finally, we confirmed that knockdown of RPARP-AS1 suppressed the malignant activity of osteosarcoma cells in vitro experiments. In general, the FRL-based prognostic signature could promote our understanding of the immune microenvironment characteristics of osteosarcoma and guide more effective treatment regimens.

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Targeting ferroptosis in osteosarcoma

Abstract: Highlights Targeting ferroptosis in osteosarcoma. A new strategy for the treatment of osteosarcoma. A non-traditional mode of regulated cell death.

Cited by 27 publications

References 87 publications

Outstanding prognostic value of novel ferroptosis-related genes in chemoresistance osteosarcoma patients

Outstanding prognostic value of novel ferroptosis-related genes in chemoresistance osteosarcoma patients

Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

Comprehensive Analysis of a Ferroptosis-Related lncRNA Signature for Predicting Prognosis and Immune Landscape in Osteosarcoma

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