Schistosoma japonicum MiRNA-7-5p Inhibits the Growth and Migration of Hepatoma Cells via Cross-Species Regulation of S-Phase Kinase-Associated Protein 2
Schistosoma japonicum MiRNA-7-5p Inhibits the Growth and Migration of Hepatoma Cells via Cross-Species Regulation of S-Phase Kinase-Associated Protein 2
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DOI：
10.3389/fonc.2019.00175
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发表时间：
2019-03-22
影响因子：
4.7
通讯作者：
Pan, Weiqing
中科院分区：
文献类型：
--
作者：
Hu, Chao;Zhu, Shanli;Pan, Weiqing
microRNAs（miRNAs）在人类疾病如癌症中发挥重要作用。人miRNA-7- 5 p是一种肿瘤抑制miRNA，通过调节多种致癌信号通路抑制肿瘤生长。近年来研究发现，植物miRNAs可以跨界调控哺乳动物基因的表达。日本血吸虫（Schistosoma japonicum）的miRNA-7- 5 p（命名为sja-miR-7- 5 p）在寄生虫和哺乳动物之间是保守的。因此，我们研究了sja-miR-7- 5 p是否具有与其哺乳动物对应物相似的抗肿瘤活性。我们首先发现sja-miR-7- 5 p在S.日本血吸虫感染sja-miR-7- 5 p模拟物在体外显著抑制小鼠和人肝癌细胞系的生长、迁移和集落形成，并诱导G1/G 0细胞周期停滞。在异种移植动物模型中，与用NC miRNA转染的那些相比，用sja-miR-7- 5 p模拟物转染的肝癌细胞接种的小鼠的肿瘤体积和重量显著降低。此外，sja-miR-7- 5 p的抗肿瘤活性是通过宿主中S期激酶相关蛋白2基因的跨物种下调来提出的。因此，sja-miR-7- 5 p在哺乳动物体内可转位至肝细胞并发挥其抗肿瘤活性，提示sja-miR-7- 5 p可能增强宿主对肝细胞癌的抵抗力。
MicroRNAs (miRNAs) play important roles in human diseases, such as cancer. Human miRNA-7-5p is a tumor suppressor miRNA that inhibits tumor growth by regulating multiple oncogenic signal pathways. Recently, studies revealed that plant miRNAs could regulate mammalian gene expression in a cross-kingdom manner. Schistosoma japonicum miRNA-7-5p (designated as sja-miR-7-5p) is conserved between the parasites and mammals. Thus, we investigated whether sja-miR-7-5p has similar antitumor activity to its mammalian counterpart. We first showed that sja-miR-7-5p was detected in host hepatocytes during S. japonicum infection. The sja-miR-7-5p mimics significantly inhibited the growth, migration, and colony formation of mouse and human hepatoma cell lines in vitro, and induced G1/G0 cell cycle arrest. In a xenograft animal model, the tumor volume and weight were significantly reduced in mice inoculated with hepatoma cells transfected with sja-miR-7-5p mimics compared with those transfected with NC miRNAs. Furthermore, the antitumor activity of sja-miR-7-5p was suggested by cross-species downregulation of the S-phase kinase-associated protein 2 gene in the host. Thus, sja-miR-7-5p is translocated into hepatocytes and exerts its anti-cancer activities in mammals, implying that sja-miR-7-5p might strengthen host resistance to hepatocellular carcinoma during schistosome infection.