Long Non-Coding RNAs Identified as Hub Genes by Weighted Gene Co-Expression Network Analysis in <i>Schistosoma mansoni</i> Following Incubation with <i>Bothrops</i> Snake Venoms

Emerging tolerance of <i>Schistosoma mansoni</i> to praziquantel, the only drug available for schistosomiasis treatment, highlights the need for new therapeutic targets. Snake venoms contain pharmacologically active proteins and peptides that can decrease the viability of <i>S. mansoni</i> worms in vitro. Long non-coding RNAs (lncRNAs) play important roles in <i>S. mansoni</i> and are promising new therapeutic targets. However, new candidates still need to be identified, as only four <i>S. mansoni</i> lncRNAs have been functionally characterized to date. Therefore, we investigated lncRNA expression changes in <i>S. mansoni</i> following incubation with <i>Bothrops</i> venoms. Adult worms were incubated with eight venoms at a sublethal dose, and phenotypic parameters were evaluated. RNA-Seq was conducted on worms incubated with <i>Bothrops jararacussu</i> or <i>Bothrops moojeni</i> venoms, followed by Weighted Gene Co-expression Network Analysis for each sex. <i>B. moojeni</i> venom reduced all phenotypic measurements, while <i>B. jararacussu</i> reduced oviposition. Both venoms altered global gene expression, including lncRNAs. Females showed two lncRNA hub genes in two venom-associated co-expression modules, while males showed 61 lncRNA hub genes in nine venom-associated modules. RT-qPCR validated six out of seven selected hub lncRNAs in male worms. These results reveal the involvement of lncRNAs in <i>S. mansoni</i> gene expression modulation induced by <i>Bothrops</i> venoms and point to lncRNAs that should be prioritized in future functional studies, such as <i>SmLINC121220-IBu</i>, <i>SmLINC152105-IBu</i> and <i>SmLNCA123831-IBu</i>.