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

Q2 Medicine

Journal of Buon Pub Date : 2021-09-01

Faliang Shi, Longyun Li, Yongjie Cheng

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引用次数: 0

Abstract

Purpose: To investigate the potential function of FAT10 in the development of osteosarcoma (OS) and its mechanism.

Methods: 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.

Results: 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.

Conclusion: FAT10 is upregulated in OS samples, which stimulates the development of OS by activating the JAK/STAT signaling pathway.

本刊更多论文

FAT10通过调控JAK/STAT信号通路刺激骨肉瘤的发展。

目的:探讨FAT10在骨肉瘤(osteosarcoma, OS)发生发展中的潜在功能及其机制。方法:采用qRT-PCR检测OS标本和细胞系中FAT10的相对水平。FAT10水平与OS患者临床特征的相关性采用χ2检验。在MG-63和U2OS细胞中干预FAT10后，分别采用qRT-PCR、CCK-8、集落形成和EdU法检测FAT10水平、细胞活力、克隆性和增殖能力的变化。采用qRT-PCR检测促炎因子诱导OS细胞中FAT10的动态变化。Western blot检测TNF-α诱导OS细胞中FAT10、p-STAT1、p-STAT3、p-STAT5蛋白水平。利用JAK2抑制剂AZ960进一步证实了JAK信号在fat10调控的OS发展中的作用。结果:FAT10在OS标本和细胞系中表达上调，与肿瘤大小、WHO分级及OS患者远处转移相关。敲低FAT10抑制MG-63和U2OS细胞的活力、克隆性和增殖能力。在IFN-γ和TNF-α刺激的OS细胞中，FAT10呈时间依赖性上调，而AZ960则呈剂量依赖性下调。AZ960诱导的OS细胞中FAT10、p-STAT1、p-STAT3和p-STAT5蛋白水平显著下调。结论:FAT10在OS样品中上调，通过激活JAK/STAT信号通路刺激OS的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Buon 医学-肿瘤学

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： JBUON aims at the rapid diffusion of scientific knowledge in Oncology. Its character is multidisciplinary, therefore all aspects of oncologic activities are welcome including clinical research (medical oncology, radiation oncology, surgical oncology, nursing oncology, psycho-oncology, supportive care), as well as clinically-oriented basic and laboratory research, cancer epidemiology and social and ethical aspects of cancer. Experts of all these disciplines are included in the Editorial Board. With a rapidly increasing body of new discoveries in clinical therapeutics, the molecular mechanisms that contribute to carcinogenesis, advancements in accurate and early diagnosis etc, JBUON offers a free forum for clinicians and basic researchers to make known promptly their achievements around the world. With this aim JBUON accepts a broad spectrum of articles such as editorials, original articles, reviews, special articles, short communications, commentaries, letters to the editor and correspondence among authors and readers. JBUON keeps the characteristics of its former paper print edition and appears as a bimonthly e-published journal with continuous volume, issue and page numbers.