Hu Chao, Li Yuzhen, Pan Danting, Wang Jing, Zhu Liufang, Lin Yu, Zhu Shanli, Pan Weiqing
Institute for Infectious Diseases and Vaccine Development, Tongji University School of Medicine, Shanghai, China.
Department of Tropical Diseases, Naval Medical University, Shanghai, China.
Front Oncol. 2021 Jun 16;11:652395. doi: 10.3389/fonc.2021.652395. eCollection 2021.
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 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 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 inhibition of tumor growth was through its anti-angiogenesis activity. Mechanically, we identified the phosphoglycerate mutase 1 () 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.
微小RNA（miRNA）是基因表达的重要调节因子。最近的研究表明，一些源自寄生虫和植物的异源miRNA能够以跨物种甚至跨界的方式调节哺乳动物基因的表达。在此，我们鉴定出一种存在于感染寄生虫的小鼠肝细胞中的miRNA（命名为sja-miR-61）。sja-miR-61模拟物显著抑制了小鼠和人肝癌细胞的迁移。在异种移植动物模型中，与对照组相比，接种了用sja-miR-61模拟物转染的肝癌细胞的小鼠的肿瘤体积和重量显著减小。我们发现肿瘤生长的抑制是通过其抗血管生成活性实现的。从机制上讲，我们鉴定出磷酸甘油酸变位酶1（PGAM1）基因是sja-miR-61的一个靶点，并发现sja-miR-61通过跨物种下调PGAM1表达介导对细胞迁移的抑制和抗血管生成作用。这些数据表明，sja-miR-61是一种肿瘤抑制性miRNA，可能对人类癌症具有治疗潜力。
