A Schistosoma japonicum MicroRNA Exerts Antitumor Effects Through Inhibition of Both Cell Migration and Angiogenesis by Targeting PGAM1.

A Schistosoma japonicum MicroRNA Exerts Antitumor Effects Through Inhibition of Both Cell Migration and Angiogenesis by Targeting PGAM1.
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DOI:
10.3389/fonc.2021.652395
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发表时间:
2021
影响因子:
4.7
通讯作者:
Pan W
Pan W
中科院分区:
医学3区
文献类型:
--
作者:
Hu C;Li Y;Pan D;Wang J;Zhu L;Lin Y;Zhu S;Pan W

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microRNA(miRNA)是基因表达的重要调控因子。近年来的研究表明,一些来源于寄生虫和植物的异源miRNAs可以跨物种甚至跨界的方式调控哺乳动物基因的表达。在这里,我们确定了一个日本血吸虫的miRNA(指定为sja-miR-61),这是目前在感染寄生虫的小鼠肝细胞。sja-miR-61模拟物在体外显著抑制小鼠和人肝癌细胞的迁移。在异种移植动物模型中,与对照相比,在接种用sja-miR-61模拟物转染的肝癌细胞的小鼠中观察到肿瘤体积和重量的显著减少。我们发现,在体内抑制肿瘤生长是通过其抗血管生成活性。从机制上讲,我们鉴定了磷酸甘油酸酯β 1(PGAM 1)基因作为sja-miR-61的靶点,并发现sja-miR-61通过跨物种下调PGAM 1表达介导了细胞迁移和抗血管生成的抑制作用。这些数据表明,sja-miR-61是一种肿瘤抑制miRNA,可能对人类癌症具有治疗潜力。
MicroRNA (miRNA) is an important regulator for gene expression. Recent studies showed that some heterogenous miRNAs derived from both parasite and plant can regulate expression of mammalian gene in a cross-species or even a cross-kingdom manner. Here, we identified a Schistosoma japonicum miRNA (designated as sja-miR-61) that is present in the hepatocyte of mice infected with the parasite. The sja-miR-61 mimics significantly inhibited the migration of both mouse and human hepatoma cells in vitro. In a xenograft animal model, significant reductions of the tumor volume and weight were observed in mice inoculated with hepatoma cells transfected with sja-miR-61 mimics compared to the controls. We found that the in vivo inhibition of tumor growth was through its anti-angiogenesis activity. Mechanically, we identified the phosphoglycerate mutase 1 (PGAM1) gene as a target of sja-miR-61 and found that the sja-miR-61-mediated suppression of cell migration and anti-angiogenesis by cross-species down-regulation of PGAM1 expression. These data indicated that sja-miR-61 is a tumor suppressor miRNA that may have therapeutic potential for human cancers.
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