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PTPRC Inhibits Ferroptosis of Osteosarcoma Cells via Blocking TFEB/FTH1 Signaling

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Abstract

Protein tyrosine phosphatase receptor type C (PTPRC) is reported to function as an oncogenic role in various cancer. However, the studies on the roles of PTPRC in osteosarcoma (OS) are limited. This study aimed to explore the potentials of PTPRC in OS. mRNA levels were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Protein expression was detected by western blot. Lysosome biogenesis was determined using immunofluorescence. The binding sites of transcription factor EB (TFEB) on the promoter of ferritin heavy chain 1 (FTH1) were predicted by the online dataset JASPAR and confirmed by luciferase and chromatin immunoprecipitation (ChIP) assays. Cell death was determined using propidium iodide (PI) and TdT-mediated dUTP nick-end labeling (TUNEL) staining. The results showed that PTPRC was significantly overexpressed in OS tissues and cells. PTPRC knockdown promoted the phosphorylation and nuclear translocation of TFEB. Moreover, PTPRC knockdown markedly promoted lysosome biogenesis and the accumulation of ferrous ion (Fe2+), whereas decreased the release of glutathione (GSH). Besides, PTPRC knockdown significantly promoted autophagy and downregulated mRNA expression of FTH1 and ferritin light chain (FTL). Additionally, TFEB transcriptionally inactivated FTH1. PTPRC knockdown significantly promoted the ferroptosis of OS cells, which was markedly alleviated by TFEB shRNA. Taken together, PTPRC knockdown-mediated TFEB phosphorylation and translocation dramatically promoted lysosome biogenesis, ferritinophagy, as well as the ferroptosis of OS cells via regulating FTH1/FTL signaling. Therefore, PTPRC/TFEB/FTH1 signaling may be a potential target for OS.

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Data Availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Jingzhou Hospital Affiliated to Yangtze University, No.26 Chuyuan Avenue, Jingzhou District, Jingzhou City, 434020, Hubei Province, China

    Yan Shao & Xiao Zuo

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  1. Yan Shao
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  2. Xiao Zuo
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Conceptualization: Yan Shao; Methodology: Xiao Zuo; Formal analysis and investigation: Yan Shao, Xiao Zuo; Writing - original draft preparation: Yan Shao, Xiao Zuo; Writing - review and editing: Yan Shao, Xiao Zuo; Resources: Yan Shao; Supervision: Xiao Zuo. Both the authors read and approved the final manuscript.

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Correspondence to Yan Shao.

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Yan Shao and Xiao Zuo contributed equally to this study.

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Shao, Y., Zuo, X. PTPRC Inhibits Ferroptosis of Osteosarcoma Cells via Blocking TFEB/FTH1 Signaling. Mol Biotechnol (2023). https://doi.org/10.1007/s12033-023-00914-9

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