The regulatory effects of p53 on the typical and atypical ferroptosis in the pathogenesis of osteosarcoma: A systematic review

Abstract

Study background: As a rare condition, osteosarcoma affects approximately 3% of all cancer patients. Its exact pathogenesis remains largely unclear. The role of p53 in up- and down-regulating atypical and typical ferroptosis in osteosarcoma remains unclear. The primary objective of the present study is investigating the role of p53 in regulating typical and atypical ferroptosis in osteosarcoma.Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Patient, Intervention, Comparison, Outcome, and Studies (PICOS) protocol were used in the initial search. The literature search was performed in six electronic databases, including EMBASE, Cochrane library of trials, Web of Science, PubMed, Google Scholar, and Scopus Review, using keywords connected by Boolean operators. We focused on studies that adequately defined patient profiles described by PICOS.Results and discussion: We found that p53 played fundamental up- and down-regulatory roles in typical and atypical ferroptosis, resulting in either advancement or suppression of tumorigenesis, respectively. Direct and indirect activation or inactivation of p53 downregulated its regulatory roles in ferroptosis in osteosarcoma. Enhanced tumorigenesis was attributed to the expression of genes associated with osteosarcoma development. Modulation of target genes and protein interactions, especially SLC7A11, resulted in enhanced tumorigenesis.Conclusion: Typical and atypical ferroptosis in osteosarcoma were regulatory functions of p53. The activation of MDM2 inactivated p53, leading to the downregulation of atypical ferroptosis, whereas activation of p53 upregulated typical ferroptosis. Further studies should be performed on the regulatory roles of p53 to unmask its possible clinical applications in the management of osteosarcoma.

Targeting Ferroptosis in Bone-Related Diseases: Facts and Perspectives

“…Mutation or inactivation of p53 can inhibit p53-SLC7A11 binding and ferroptosis in OS cells. 166 p53 also regulates cellular ROS, iron and lipids. Flavonoids bavachin can inhibit signal transducer and activator of transcription 3 (STAT3) phosphorylation, promote p53 and inhibit SLC7A11 expression through STAT3-p53-SLC7A11 axis.…”

Translational Potential of Baicalein in Mitigating RSL3-Induced Ferroptosis in Fibroblasts: Implications for Therapeutic Interventions

“…The gene expression of these factors can be influenced by various signaling pathways and transcriptional regulators involved in ferroptosis. These include nuclear factor erythroid 2-related factor 2 (Nrf2) 18 - 21 , the ferroptosis suppressor protein glutathione peroxidase 4 (GPX4) 22 - 24 , the tumor suppressor protein p53 25 - 27 , and System xc-, a cystine-glutamate antiporter consisting of solute carrier (SLC)3A2 and SLC7A11, which is crucial for importing cystine into the cell in exchange for glutamate 28 , 29 . The small-molecule compound rat sarcoma virus-selective lethal 3 (RSL3) is frequently employed as a ferroptosis activator, inhibits the function of GPX4, and causes a buildup of lipid peroxides, which initiates a chain reaction of lipid peroxidation.…”