Abstract
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.
Highlights
The primary pathology of schistosomiasis caused by S. japonicum is egg-induced granuloma and fibrosis
We demonstrated that sja-miR-7-5p is present in hepatocytes during the S. japonicum infection and the sja-miR-7-5p exerts anticancer effects on multiple hepatoma cells by targeting the S-phase kinase-associated protein 2(SKP2) gene, which is a component of the SCF (Skp1-Cullin 1-F-box) E3 ubiquitin-ligase complex
Hsa-miR-7-5p is well-characterized as a tumor suppressor miRNA that suppresses survival, proliferation, invasion, and migration of multiple cancer cells, as well as increasing the sensitivity of resistant tumor cells to therapeutics
Summary
The primary pathology of schistosomiasis caused by S. japonicum is egg-induced granuloma and fibrosis. Aberrant miRNA expression promotes the occurrence and development of various cancers [6,7,8]; some miRNAs can exert therapeutic effects on multiple cancers through regulation of tumor-related genes, including those that control tumor cell growth or apoptosis [9, 10]. MiRNAs derived from plants can regulate the expression of their target genes in mammals in a cross-kingdom manner [11,12,13]. Accumulating evidence indicates that heterogeneous miRNAs can modulate cell functions in mammals. It remains unclear how the plant miRNAs can survive the passage through the gastrointestinal tract following ingestion
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