Project description:Cancer remains positioned as the leading cause of death worldwide, with nearly 10 million deaths and an estimated 20 million new cases yearly. Here, we present analyses of molecular data from the tumor-suppressing larvae of the tapeworm Mesocestoides corti, the intraperitoneal infection of which has previously demonstrated the ability to abrogate the growth and metastasis of the highly aggressive B16F10 melanoma in mice. In order to explore the potential effector mechanisms and molecules behind its cancer-suppressive capabilities, we analyzed the M. corti larval transcriptome in the C57BL/6J and ICR mouse strains, as well as in vitro, and the proteomic profiles of whole worm homogenate and its excretory-secretory products. We present, thus far, the most extensive list of experimentally verified M. corti protein products. These were searched for molecules potentially responsible for the tapeworm’s immune-related cancer-suppressive abilities. Many proteins with potential immunomodulatory properties were found within its proteome, including those from the cysteine-rich secretory CAP family, such as GLIPR-like proteins. Furthermore, functional tests of McKI-C1, an ortholog of the anti-cancer Kunitz inhibitor EgKI-1 from Echinococcus granulosus, were performed both in vitro and in vivo, to ascertain whether it could express a similar effect. While McKI-C1 did not show itself as an effector molecule in the tapeworm’s cancer-suppressive abilities, the extensive list of potentially functional molecules prompts further exploration.
Project description:MicroRNAs (miRNAs), a class of small non-coding RNAs, are key regulators of gene expression at post-transcriptional level and play essential roles in fundamental biological processes such as metabolism and development. The particular developmental characteristics of cestode parasites highlight the importance of studying miRNA gene regulation in these organisms. Here, we performed a comprehensive analysis of miRNAs in two developmental stages of the model cestode Mesocestoides corti. Using a high-throughput sequencing approach, we found transcriptional evidence of 42 miRNA loci in tetrathyridia larvae and strobilated worms. Tetrathyridium and strobilated worm-specific miRNAs were found, as well as differentialy expressed miRNAs between these developmental stages, suggesting miRNA regulation of stage-specific features. Moreover, it was shown that uridylation is a differential mechanism of post-transcriptional modification of M. corti miRNAs. The whole set of M. corti miRNAs represent 33 unique miRNA families, and confirm the remarkable loss of conserved miRNA families within platyhelminth parasites, reflecting their relatively low morphological complexity and high adaptation to parasitism. Overall, the presented results provide a valuable platform to studies aiming to identify and characterize novel miRNA-based molecular mechanisms of post-transcriptional gene regulation in cestodes, necessary for the elucidation of developmental aspects of the complex biology of these parasites.
Project description:Genomic assembly of cestode Mesocestoides corti, as part of the 50 Helminth Genomes Initiative sequencing of the parasitic worms that have the greatest impact on human, agricultural and veterinary disease and cause significant global health issues particularly in the developing world, or those used as model organisms.
Project description:Clarify changes in chromatin accessibility regions after Bmi1 knockout by performing ATAC-seq on Bmi1 KO and WT organ of Corti from neonatal mice, providing a foundation for integrated analysis of epigenetics and transcriptome sequencing"
