Transcriptome Profiling and ceRNA Network of Small Extracellular Vesicles from Resting and Degranulated Mast Cells

Abstract

Aim: This study aimed to investigate the transcriptomic characteristics and interactions between competitive endogenous RNAs (ceRNAs) within small extracellular vesicles (sEVs) derived from mast cells (MCs). Methods: Transcriptome sequencing analyzed lncRNA, circRNA and mRNA expression in resting and degranulated MC-derived sEVs. Constructed ceRNA regulatory network through correlation analysis and target gene prediction. Results: Differentially expressed 1673 mRNAs, 173 lncRNAs and 531 circRNAs were observed between resting and degranulated MCs-derived sEVs. Enrichment analysis revealed involvement of neurodegeneration, infection and tumor pathways. CeRNA networks included interactions between lncRNA–miRNA, circRNA–miRNA and miRNA–mRNA, targeting genes in the hippo and wnt signaling pathways linked to tumor immune regulation. Conclusion: This study provides valuable insights into MC-sEV molecular mechanisms, offering significant data resources for further investigations.

Plain language summary

Mast cells (MCs) are important for various health conditions, including allergies, infections, tumors and brain disorders. MCs release tiny structures called small extracellular vesicles (sEVs) that carry different molecules, such as genetic material, to communicate with other cells in the body’s immune system. However, we still do not know much about how these sEVs work. In this study, we examined the sEVs from MCs and found specific genetic molecules that change when MCs become activated. We discovered that these molecules are involved in important processes related to diseases like neurodegeneration and infection. We also identified networks of molecules that interact with each other, influencing immune regulation of tumor. By studying this, we gain new knowledge about how MCs use sEVs to communicate with other cells in our body during immune responses.

Tweetable abstract

Decoding mast cell messages: Explore the world of small extracellular vesicles (sEVs) and their genetic communication. Discover connections between lncRNAs, circRNAs and mRNAs in MC-derived sEVs, and implications for neurodegeneration, infection, and tumor immune regulation.

Keywords::

• ceRNA network
• circRNA
• extracellular vesicle
• lncRNA
• mast cell
• mRNA

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2023-0175

Author contributions

LL and Y Liang initiated and supervised this study. L Lin performed experiments, analyzed data and drafted manuscript. T Cao and Y Huang identified extracellular vesicles. J Li and J Wang validated the sequencing data. X Peng, Y Ge and Y Li provided technical support. All authors approved the submitted manuscript. L Lin and Y Liang contributed equally to this work and should be considered co-first authors.

Acknowledgments

The authors thank CloudSeq Biotech (Shanghai, China) for providing sEV transcriptome sequencing services. They further acknowledge Linfang Deng (Changzhou Institute of Technology) for the help during the study.

Financial disclosure

This work was financially supported by National Natural Science Foundation of China (grant nos. 81871267, 81401335); Shanghai Hospital Development Center (grant no. SHDC2020CR3007A); Shanghai Science and Technology Commission (grant no. 19441904300). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical disclosure

The authors state that the animal experiments in this study were carried out under the approval of the Animal Ethics Committee of Shanghai Jiaotong University School of Medicine.