Wang Linfeng, Pan Su
Department of Orthopedic Surgery, The Second Hospital of Jilin University, Changchun, China.
Front Genet. 2023 Mar 29;14:1154299. doi: 10.3389/fgene.2023.1154299. eCollection 2023.
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. 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. 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. 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.
作为一种罕见疾病，骨肉瘤影响约3%的所有癌症患者。其确切发病机制在很大程度上仍不清楚。p53在骨肉瘤中上调和下调非典型和典型铁死亡中的作用仍不清楚。本研究的主要目的是探讨p53在调节骨肉瘤中典型和非典型铁死亡中的作用。在初始检索中使用了系统评价和Meta分析的首选报告项目（PRISMA）以及患者、干预措施、对照、结局和研究（PICOS）方案。在六个电子数据库中进行文献检索，包括EMBASE、Cochrane试验库、科学网、PubMed、谷歌学术和Scopus综述，使用由布尔运算符连接的关键词。我们关注充分定义了PICOS描述的患者概况的研究。我们发现p53在典型和非典型铁死亡中发挥着基本的上调和下调作用，分别导致肿瘤发生的促进或抑制。p53的直接和间接激活或失活下调了其在骨肉瘤铁死亡中的调节作用。肿瘤发生增强归因于与骨肉瘤发展相关的基因表达。靶基因和蛋白质相互作用的调节，尤其是SLC7A11，导致肿瘤发生增强。骨肉瘤中的典型和非典型铁死亡是p53的调节功能。MDM2的激活使p53失活，导致非典型铁死亡下调，而p53的激活上调典型铁死亡。应进一步研究p53的调节作用，以揭示其在骨肉瘤治疗中可能的临床应用。
