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

Emerging tolerance of Schistosoma mansoni 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 S. mansoni worms in vitro. Long non-coding RNAs (lncRNAs) play important roles in S. mansoni and are promising new therapeutic targets. However, new candidates still need to be identified, as only four S. mansoni lncRNAs have been functionally characterized to date. Therefore, we investigated lncRNA expression changes in S. mansoni following incubation with Bothrops 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 Bothrops jararacussu or Bothrops moojeni venoms, followed by Weighted Gene Co-expression Network Analysis for each sex. B. moojeni venom reduced all phenotypic measurements, while B. jararacussu 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 S. mansoni gene expression modulation induced by Bothrops venoms and point to lncRNAs that should be prioritized in future functional studies, such as SmLINC121220-IBu, SmLINC152105-IBu and SmLNCA123831-IBu.