Identification of a Schistosoma japonicum MicroRNA That Suppresses Hepatoma Cell Growth and Migration by Targeting Host FZD4 Gene.
Identification of a Schistosoma japonicum MicroRNA That Suppresses Hepatoma Cell Growth and Migration by Targeting Host FZD4 Gene.
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DOI：
10.3389/fcimb.2022.786543
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发表时间：
2022
影响因子：
5.7
通讯作者：
Pan W
中科院分区：
文献类型：
--
作者：
Jiang P;Wang J;Zhu S;Hu C;Lin Y;Pan W
以往的研究表明，来自植物和寄生虫的miRNAs可以跨王国的方式调节哺乳动物的基因表达和细胞表型，导致疾病的发生或增强宿主对癌症等疾病的抵抗力。在本研究中，我们通过筛选57个具有体外和体内抗肿瘤活性的日本血吸虫miRNA，鉴定了一个血吸虫miRNA(命名为SJA-miR-71a)。我们证明了这种寄生虫miRNA在感染期间存在于肝细胞中。我们发现SJA-miR-71a在体外将肝癌细胞株的细胞周期阻滞在G0/G1期，并抑制细胞增殖。转染SJA-miR-71a模拟物的HepG2细胞的迁移和集落形成明显减少。此外，在异种小鼠模型中，转染SJA-miR-71a模拟物的肿瘤细胞的生长明显受到抑制。机制上，我们发现SJA-miR-71a的抗肿瘤活性是通过靶向编码Frizzled4类受体(FZD4)的宿主基因实现的，因为FZD4小干扰RNA(SiRNAs)对肿瘤产生了类似的抑制作用。这些数据表明SJA-miR-71a是一种肿瘤抑制因子miRNA，并提示这种寄生虫来源的miRNA可能成为癌症的治疗靶点。
Previous studies have demonstrated miRNAs derived from plants and parasites can modulate mammalian gene expression and cell phenotype in a cross-kingdom manner, leading to occurrence of diseases or strengthening resistance of host to diseases such as cancer. In this study, we identified a schistosome miRNA (named Sja-miR-71a) through screening of 57 Schistosoma japonicum miRNAs that exerts antitumor activity in vitro and in vivo models. We demonstrated presence of this parasite miRNA in liver cells during infection. We showed that Sja-miR-71a arrested cell cycle at G0/G1 phase of hepatoma cell lines and inhibited cell proliferation in vitro. The HepG2 transfected with Sja-miR-71a mimics displayed significant reduction of migration and colony formation. Further, growth of the tumor cells transfected with the Sja-miR-71a mimics was obviously suppressed in a xenograft mouse model. Mechanically, we found the antitumor activity of Sja-miR-71a was through targeting a host gene encoding Frizzled Class Receptor 4 (FZD4), as FZD4 small interfering RNAs (siRNAs) generated a similar inhibitory effect on the tumor. These data indicated that Sja-miR-71a is a tumor suppressor miRNA and suggested this parasite-derived miRNA as a potential therapeutic target for cancer.