FAT10 stimulates the development of osteosarcoma by regulating the JAK/STAT signaling pathway.

To investigate the potential function of FAT10 in the development of osteosarcoma (OS) and its mechanism. Relative level of FAT10 in OS specimens and cell lines was detected by qRT-PCR. The correlation between FAT10 level and clinical features of OS patients was assessed by χ2 test. After intervention of FAT10 in MG-63 and U2OS cells, changes of FAT10 level, cell viability, clonality and proliferative capacity were respectively detected by qRT-PCR, CCK-8, colony formation and EdU assay. Moreover, dynamic change of FAT10 in OS cells induced with pro-inflammatory factors was examined by qRT-PCR. Protein levels of FAT10, p-STAT1, p-STAT3 and p-STAT5 in OS cells induced with TNF-α were determined by Western blot. The JAK2 inhibitor AZ960 was used to further confirm the role of the JAK signaling in FAT10-regulated development of OS. FAT10 was upregulated in OS specimens and cell lines, which was correlated to tumor size, WHO grade and distant metastasis of OS patients. Knockdown of FAT10 inhibited viability, clonality and proliferative capacity of MG-63 and U2OS cells. FAT10 was time-dependently upregulated in OS cells stimulated with IFN-γ and TNF-α, which was dose-dependently downregulated by the treatment of AZ960. Protein levels of FAT10, p-STAT1, p-STAT3 and p-STAT5 in OS cells induced with AZ960 were remarkably downregulated. FAT10 is upregulated in OS samples, which stimulates the development of OS by activating the JAK/STAT signaling pathway.

Citation

Faliang Shi, Longyun Li, Yongjie Cheng. FAT10 stimulates the development of osteosarcoma by regulating the JAK/STAT signaling pathway. Journal of B.U.ON. : official journal of the Balkan Union of Oncology. 2021 Sep-Oct;26(5):2090-2096

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PMID: 34761621

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