IMPAM   23988
INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Premio Mejor Comunicación Oral: MicroRNAs in parasitic cestodes: discovery, functional analysis and role in host-parasite communication
Autor/es:
CUCHER M; MALDONADO L; PÉREZ MG; KAMENETZKY L; MACCHIAROLI N; ANCAROLA E; ROSENZVIT M C
Lugar:
BUENOS AIRES
Reunión:
Jornada; Jornadas 2016 de la SAB: Codificar o no codificar: rol de ARN no codificantes en la fisiología y la patología; 2016
Resumen:
MicroRNAs IN PARASITIC CESTODES: DISCOVERY, FUNCTIONAL ANALYSIS AND ROLE IN HOST-PARASITE COMMUNICATIONMacchiaroli N, Cucher M, Pérez M, Ancarola M E, Maldonado L, Kamenetzky L, Rosenzvit M CIMPaM CONICET-UBA, Buenos Aires, Argentina. E-mail: mrosenzvit@fmed.uba.arTapeworms (Cestoda) are etiological agents of neglected diseases such as hydatidosis and neurocysticercosis, caused by the larval stages of Echinococcus and Taenia solium, respectively. Understanding the mechanisms that regulate their particular characteristics of development and survival in the host may allow identifying new therapeutic targets. MicroRNAs are small silencing RNAs that impact eukaryotic development and are receiving growing attention as novel therapeutic and diagnosis targets. Our team identified miRNAs in cestodes for the first time and reported differential expression among developmental stages and species with diverse developmental and morphological characteristics by means of smallRNAseq and big data analysis at the Bioinformatic Node at IMPaM. We performed prediction of miRNA targets by an integrated bioinformatics pipeline that included 3?UTR annotation and RNAseq data analysis. In this way, 941 potential miRNA target sites distributed in 724 3?UTRs were found in Echinococcus canadensis. Most of them were found to be conserved among species of the genus Echinococcus, adding confidence to the predictions obtained. Functional analysis of miRNA targets showed that MAPK and WNT signaling pathways were among the most represented, suggesting miRNA roles in parasite growth and development. In order to know if miRNAs are secreted by cestode parasites and could represent a way of parasite-host communication, we searched for extracellular vesicles (EVs) in 2 model cestode parasites: Taenia crassiceps and Mesocestoides corti. As a result, we demonstrated the in vitro secretion of membranous structures compatible with EVs by transmission electron microscopy and identified, by proteomics approach, expected eukaryotic EV markers and also, among others, proteins used for immunodiagnosis of cestode infection as well as host immunoglobulins. Finally, we proved by capillary electrophoresis that cestode EVs carry small RNAs and then microRNAs were detected by RT-(q)PCR. In conclusion, miRNAs have emerged as the main smallRNA silencing molecules in cestodes being several of them absent in the host or highly divergent with respect to host orthologs. In addition, important pathways were predicted to be targeted by miRNAs. Also, these small RNA regulators were shown to be secreted in EVs, and could thus be involved in host-parasite communication. These results suggest that miRNAs are candidates for novel diagnosis and therapeutic interventions against parasitic neglected diseases and pave the way for further functional studies.