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Schistosoma japonicum sja-let-7 Inhibits the Growth of Hepatocellular Carcinoma Cells via Cross-Species Regulation of Col1α2

文献类型： 外文期刊

作者： Zhong, Haoran 1 ; Dong, Bowen 1 ; Zhu, Danlin 1 ; Fu, Zhiqiang 1 ; Liu, Jinming 1 ; Guan, Guiquan 2 ; Jin, Yamei 1 ;

作者机构： 1.Chinese Acad Agr Sci, Shanghai Vet Res Inst, Natl Reference Lab Anim Schistosomiasis, Key Lab Anim Parasitol Minist Agr & Rural Affairs, Shanghai 200241, Peoples R China

2.Chinese Acad Agr Sci, Lanzhou Vet Res Inst, State Key Lab Anim Dis Control & Prevent, Key Lab Vet Parasitol Gansu Prov, Lanzhou 730046, Peoples R China

关键词： liver fibrosis; hepatocellular carcinoma; schistosome; sja-let-7; Col1 alpha 2

期刊名称：GENES （ 影响因子：2.8； 五年影响因子：3.2 ）

ISSN：

年卷期： 2024 年 15 卷 9 期

页码：

收录情况： SCI

摘要： 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 Schistosoma japonicum extracellular vesicles (EVs) deliver sja-let-7 to hepatic stellate cells, leading to the inhibition of Col1 alpha 2 expression and alleviation of liver fibrosis. Given the well-documented antifibrotic and antiproliferative properties of the let-7 miRNA family, this study aims to preliminarily investigate the effects of the sja-let-7/Col1 alpha 2 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 Col1 alpha 2 in extracellular matrix organization. Pan-cancer analysis revealed that Col1 alpha 2 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 sja-let-7 mimics significantly reduced Col1 alpha 2 expression, inhibited HCC cell proliferation, migration, and colony formation. These findings suggest that sja-let-7, by targeting Col1 alpha 2, has the potential to serve as a therapeutic agent in HCC treatment. This study indicates the pivotal role of Col1 alpha 2 in liver fibrosis and HCC, and the promising therapeutic application of helminth-derived miRNAs.

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