Project description:The excretory-secretory proteins (ESPs) of Trichinella spiralis (T. spiralis) muscle larvae have been confirmed to exert antitumor effects by modulating host immune responses or directly acting on tumor cells. Our research group previously identified that the ESPs of T. spiralis muscle larvae contain multiple proteins potentially related to antitumor activity, among which tropomyosin (TM) has attracted our attention. This study aims to introduce TM from Trichinella spiralis (T. spiralis TM) into breast cancer MCF-7 cells via transfection technology. Furthermore, we investigated the impact of T. spiralis TM on the gene expression profile of MCF-7 cells through transcriptomics. Finally, the study systematically evaluated its regulatory effects on apoptosis, proliferation, and migration. We are the first to comprehensively evaluated the anticancer effects of T. spiralis TM on MCF-7 breast cancer cells. Our findings showed that T. spiralis TM increases apoptosis by activating the mitochondrial-mediated apoptosis pathway and inhibits cell migration and proliferation by downregulating the expression of important hub genes, including PRKACA, CDK3, VPS35, and BCAR1. These findings provide a novel theoretical basis for the application of molecules linked to Trichinella in tumor therapy and support for potential new targets.
Project description:A growing body of evidence in mammalian cells indicates that secreted vesicles can be used to mediate intercellular communication processes by transferring various bioactive molecules, including mRNAs and microRNAs. Based on these findings, we decided to analyze whether T. cruzi-derived extracellular vesicles contain RNA molecules and performed a deep sequencing and genome-wide analysis of a size-fractioned cDNA library (16M-bM-^@M-^S40 nt) from extracellular vesicles secreted by noninfective epimastigote and infective metacyclic trypomastigote forms. Our data show that the small RNAs contained in these extracellular vesicles originate from multiple sources, including tRNAs. In addition, our results reveal that the variety and expression of small RNAs are different between parasite stages, suggesting diverse functions. Taken together, these observations call attention to the potential regulatory functions that these RNAs might play once transferred between parasites and/or to mammalian host cells. Small RNAs profiles (16-40 nt) of epimastigote-derived extracellular vesicles, metacyclic trypomastigote-derived extracellular vesicles and metacyclic trypomastigote parental cells.
Project description:Trichinellosis of human and other mammals was caused through the ingestion of the parasite,Trichinella spiralis,contaminated meat. It is a typical zoonotic disease that affects more than 10 million people world-wide. Parasites of Trichinella genus are unique intracellular pathogens. Adult Trichinella parasites directly release newborn larvae which invade striated muscle cells and causes diseases. In this study, we profiled the global transcriptome in the three developmental stages of T. spiralis. The transcriptomic analysis revealed the global gene expression patterns from newborn larval stage through muscle larval stage to adults. Thousands of genes with stage-specific transcriptional patterns were described and novel genes involving host-parasite interaction were identified. More than 45% of the protein-coding genes showed evidence of transcription from both sense and antisense strands which suggests the importance of RNA-mediated gene regulation in the parasite. This study presents a first deep analysis of the transcriptome of T. spiralis, providing insight information of the parasite biology.
Project description:We describe the first comprehensive study confirming the existence of DNA methylation, characterising the methylomes of three life stages of the food-borne agent of human trichinellosis, Trichinella spiralis. We further identify sets of genes where the DNA methylation status varied between thedevelopmental stages that are closely related to the parasitism of the organism. Examination of DNA methylation status in three life stages (Adult, muscle larve, new born larve) of Trchinella Spiralis using MethylC-seq.
Project description:Similar to bacterial proteins that are targeted to distinct macrophages organelles via extracellular vesicles, we propose that these vesicles also traffic small RNAs to modulate specific host factors. To test this, we aim to sequence extracellular vesicle derived sRNA, and whole bacterial small RNAs to determine selectivity, and to identify their bacterial and mammalian targets (Experimental Plan in Table-1). For this we will collect highly purified vesicles from N. gonorrhoeae (strain MS11A). We will also treat mouse derived primary macrophages with extracellular vesicles and compare their RNA response to untreated macrophages (Table-2). This will provide novel insights into how macrophages respond to N. gonorrhoeae infections. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Project description:Objective. To investigate the epigenetic footprint of idiopathic inflammatory myopathies (IIM) through characterization of circulating extracellular vesicles (EVs) and the expression of EV-derived small non-coding RNAs (sncRNAs).
Project description:A growing body of evidence in mammalian cells indicates that secreted vesicles can be used to mediate intercellular communication processes by transferring various bioactive molecules, including mRNAs and microRNAs. Based on these findings, we decided to analyze whether T. cruzi-derived extracellular vesicles contain RNA molecules and performed a deep sequencing and genome-wide analysis of a size-fractioned cDNA library (16–40 nt) from extracellular vesicles secreted by noninfective epimastigote and infective metacyclic trypomastigote forms. Our data show that the small RNAs contained in these extracellular vesicles originate from multiple sources, including tRNAs. In addition, our results reveal that the variety and expression of small RNAs are different between parasite stages, suggesting diverse functions. Taken together, these observations call attention to the potential regulatory functions that these RNAs might play once transferred between parasites and/or to mammalian host cells.
Project description:In mammalian systems, extracellular small RNAs can operate in a paracrine manner to communicate information between cells, relying on transport within vesicles. “Foreign” small RNAs derived from bacteria, plants and parasites have also been detected in mammalian body fluids, sparking interest in whether these could mediate inter-species communication. However, there is no mechanistic framework for RNA-mediated interspecies communication and the active movement of RNA via vesicles has not been shown outside of mammals. Here we demonstrate that specific microRNAs and Y RNAs are packaged into vesicles secreted by a gastrointestinal nematode, Heligmosomoides polygyrus, which naturally infects mice. Total RNA was extracted from the secretion product of adult worms and compared to the profile of small RNAs in adult worms, eggs and infective larvae.
Project description:In mammalian systems, extracellular small RNAs can operate in a paracrine manner to communicate information between cells, relying on transport within vesicles. “Foreign” small RNAs derived from bacteria, plants and parasites have also been detected in mammalian body fluids, sparking interest in whether these could mediate inter-species communication. However, there is no mechanistic framework for RNA-mediated interspecies communication and the active movement of RNA via vesicles has not been shown outside of mammals. Here we demonstrate that specific microRNAs and Y RNAs are packaged into vesicles secreted by a gastrointestinal nematode, Heligmosomoides polygyrus, which naturally infects mice.