National Reference Laboratory for Animal Schistosomiasis, Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Science, Lanzhou 730046, China.
Genes (Basel). 2024 Sep 4;15(9):1165. doi: 10.3390/genes15091165.
Liver fibrosis, a critical precursor to hepatocellular carcinoma (HCC), results from chronic liver injury and significantly contributes to HCC progression. Schistosomiasis, a neglected tropical disease, is known to cause liver fibrosis; however, this process can be modulated by schistosome-derived miRNAs. Previous studies from our laboratory have demonstrated that extracellular vesicles (EVs) deliver to hepatic stellate cells, leading to the inhibition of expression and alleviation of liver fibrosis. Given the well-documented antifibrotic and antiproliferative properties of the miRNA family, this study aims to preliminarily investigate the effects of the axis on BALB/c mice and HCC cell line SNU387, providing a basis for the potential application of parasite-derived molecules in HCC therapy. In the present study, schistosome-induced fibrosis datasets were analyzed to identify the role of in extracellular matrix organization. Pan-cancer analysis revealed that is upregulated in various cancers, including HCC, with significant associations with immune cell infiltration and clinical parameters, highlighting its diagnostic importance. Functional assays demonstrated that transfection with mimics significantly reduced expression, inhibited HCC cell proliferation, migration, and colony formation. These findings suggest that , by targeting , has the potential to serve as a therapeutic agent in HCC treatment. This study indicates the pivotal role of in liver fibrosis and HCC, and the promising therapeutic application of helminth-derived miRNAs.
肝纤维化是肝细胞癌（HCC）的关键前体，由慢性肝损伤引起，是 HCC 进展的重要原因。血吸虫病是一种被忽视的热带病，已知会导致肝纤维化；然而，这一过程可以通过血吸虫来源的 miRNAs 进行调节。我们实验室的先前研究表明，细胞外囊泡（EVs）将 miRNA 传递到肝星状细胞，导致 miRNA 表达抑制和肝纤维化缓解。鉴于 miRNA 家族有充分记载的抗纤维化和抗增殖特性，本研究旨在初步研究 miRNA 轴对 BALB/c 小鼠和 HCC 细胞系 SNU387 的影响，为寄生虫来源的分子在 HCC 治疗中的潜在应用提供依据。在本研究中，分析了血吸虫诱导的纤维化数据集，以确定 miRNA 在细胞外基质组织中的作用。泛癌症分析显示，miRNA 在包括 HCC 在内的各种癌症中上调，与免疫细胞浸润和临床参数有显著关联，突出了其诊断重要性。功能分析表明，miRNA 模拟物的转染显著降低了 miRNA 的表达，抑制了 HCC 细胞的增殖、迁移和集落形成。这些发现表明，miRNA 通过靶向，有可能成为 HCC 治疗的治疗剂。本研究表明 miRNA 在肝纤维化和 HCC 中的关键作用，以及寄生虫来源的 miRNAs 的有前途的治疗应用。
