Project description:RNA modifications play important roles in cellular processes, and their dysregulation has been linked to various diseases, including cancer. As extracellular vesicles (EVs) contain various RNAs, it is assumed that these can be modified. However, the presence of such modified transcripts has not been determined due to the small amount of RNAs in EVs. Herein, we successfully detected 22 RNA modifications in EVs using a proprietary ultra-high performance liquid chromatography tandem mass spectrometry system and identified reduced levels of N6-methyladenosine (m6A) in EVs derived from colon cancer tissues, which correlated with cancer recurrence. Increasing m6A modification levels in colorectal cancer EVs via m6A demethylase Alkbh5 knockout suppressed the tumor-promoting effect of colorectal cancer EVs. Mechanistically, colorectal cancer-derived EVs increased tumor necrotic factor a and interleukin-6 secretion by macrophages via toll-like receptor 8 in an m6A-dependent manner and promoted cancer cell proliferation. RNA-seq analysis showed that 5’-tRF-GlyGCC were enriched in colorectal cancer EVs, and m6A levels on 5’-tRF-GlyGCC were decreased in colorectal cancer EVs compared with those in normal colon EVs. Cancer-derived EVs containing 5’-tRF-GlyGCC significantly promoted tumor growth, and the effect was impeded through macrophage depletion. These data provide evidence that cancer-specific RNA modifications are present in EVs, promoting tumor progression by regulating immune cells.
Project description:To examine the effect of tumor-derived small extracellular vesicles on Meso-CAR T cells. Series of genes of CAR T cells treated with or without tumor-derived small extracellular vesicles were detected.
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:Background: There is some evidence demonstrating the effect of psychological interventions in improvements in health biological parameters. To best of our knowledge, no study had addressed the impact of any psychological intervention on extracellular vesicles. In addition, Mindfulness-Based Cognitive Therapy (MBCT) and Emotion Focused Therapy for Cancer Recovery (EFT-CR) in the group have never been explored regarding extracellular vesicles and the effectiveness of these was not compared yet.
Objectives:
1. To explore and compare the effect of MBCT and EFT-CR on biological parameters and psychological variables in distressed people who have had breast, prostate and colorectal cancer;
2. In addition, we will explore the acceptability through recruitment and retention rates of MBCT and EFT-CR in group and evaluate whether these interventions are appropriate for a larger clinical trial.
Methods: The design of this study is a parallel randomized controlled trial. Participants will be randomized into MBCT, EFT-CR or usual care. Outcome measures will be assessed before, at the end of the intervention (8 weeks) and follow-ups (24 and 52 weeks from the baseline moment).
Hypotheses: The researchers expected that both interventions will have an effect on extracellular vesicles and other study biomarkers as well as improvements in psychological outcomes, compared to treatment as usual (TAU) group. Regarding the comparative effectiveness, we did not have evidence to hypothesize which one of the interventions will be superior in both biological (extracellular vesicles) and psychological outcomes.
Contribution for practice: The results of this preliminary study would permit to know if there are benefits of these psychological interventions on changes in extracellular vesicles and on psychological outcomes related to health. In addition, this study will permit to determine the acceptability of conducting a larger randomized controlled trial.
Project description:Plasmodium falciparum secretes extracellular vesicles that contain RNA. The biological benefit of this secretion to the secreting parasite is not known. Here, we sequenced the RNA content of extracellular vesicles and compared with that of the secreting whole parasites. The data suggests that extracellular vesicles might be part of a post-transcriptional regulatory mechanism that shapes intracellular RNA levels in the parasite.
Project description:To gain insight into the microRNA expression profile of small extracellular vesicles derived from bone metabolism related cell types and to verify their mechanism, we utilized the miRNA sequencing technology to analyze the miRNA profiles of different mouse osteoblast and osteoclast cell derived small extracellular vesicles.
Project description:Transcriptional comparison of B16F10 cells with B16F10 cell-derived extracellular vesicles (EVs) to identify transcripts enriched or de-enriched in EVs compared to their donor cells.