MicroRNA-Transcription factor regulatory networks in the early strobilar development of Echinococcus granulosus protoscoleces

MOHAMMADI, MOHAMMAD ALI; MANSOURI, MEHDI; DERAKHSHANI, ALI; REZAIE, MASOUD; BORHANI, MEHDI; NASIBI, SAEID; MOUSAVI, SEYED MOHAMMAD; AFGAR, ALI; MACCHIAROLI, NATALIA; ROSENZVIT, MARA C.; HARANDI, MAJID FASIHI

BMC GENOMICS

BIOMED CENTRAL LTD

Año: 2023 vol. 24

1471-2164

Background Echinococcus granulosus sensu lato has a complex developmental biology with a variety of factorsrelating to both intermediate and final hosts. To achieve maximum parasite adaptability, the development of thecestode is dependent on essential changes in transcript regulation. Transcription factors (TFs) and miRNAs are knownas master regulators that affect the expression of downstream genes through a wide range of metabolic and signalingpathways. In this study, we aimed to develop a regulatory miRNA-Transcription factor (miRNA-TF) network across earlydevelopmental stages of E. granulosus protoscoleces by performing in silico analysis, and to experimentally validateTFs expression in protoscoleces obtained from in vitro culture, and from in vivo experiments.Results We obtained list of 394 unique E. granulosus TFs and matched them with 818 differentially expressed geneswhich identified 41 predicted TFs with differential expression. These TFs were used to predict the potential targets of31 differentially expressed miRNAs. As a result, eight miRNAs and eight TFs were found, and the predicted networkwas constructed using Cytoscape. At least four miRNAs (egr-miR-124a, egr-miR-124b-3p, egr-miR-745-3p, andegr-miR-87-3p) and their corresponding differentially expressed TFs (Zinc finger protein 45, Early growth responseprotein 3, Ecdysone induced protein 78c and ETS transcription factor elf 2) were highlighted in this investigation.The expression of predicted differentially expressed TFs obtained from in vitro and in vivo experiments, wereexperimentally validated by quantitative polymerase chain reaction. This confirmed findings of RNA-seq data.Conclusion miRNA-TF networks presented in this study control some of the most important metabolic and signalingpathways in the development and life cycle of E. granulosus, providing a potential approach for disrupting the earlyhours of dog infection and preventing the development of the helminth in the final host.