Extracellular vesicles in gastric cancer: role of exosomal lncRNA and microRNA as diagnostic and therapeutic targets

Abstract

Extracellular vesicles (EVs), including exosomes, play a crucial role in intercellular communication and have emerged as important mediators in the development and progression of gastric cancer. This review discusses the current understanding of the role of EVs, particularly exosomal lncRNA and microRNA, in gastric cancer and their potential as diagnostic and therapeutic targets. Exosomes are small membrane-bound particles secreted by both cancer cells and stromal cells within the tumor microenvironment. They contain various ncRNA and biomolecules, which can be transferred to recipient cells to promote tumor growth and metastasis. In this review, we highlighted the importance of exosomal lncRNA and microRNA in gastric cancer. Exosomal lncRNAs have been shown to regulate gene expression by interacting with transcription factors or chromatin-modifying enzymes, which regulate gene expression by binding to target mRNAs. We also discuss the potential use of exosomal lncRNAs and microRNAs as diagnostic biomarkers for gastric cancer. Exosomes can be isolated from various bodily fluids, including blood, urine, and saliva. They contain specific molecules that reflect the molecular characteristics of the tumor, making them promising candidates for non-invasive diagnostic tests. Finally, the potential of targeting exosomal lncRNAs and microRNAs as a therapeutic strategy for gastric cancer were reviewed as wee. Inhibition of specific molecules within exosomes has been shown to suppress tumor growth and metastasis in preclinical models. In conclusion, this review article provides an overview of the current understanding of the role of exosomal lncRNA and microRNA in gastric cancer. We suggest that further research into these molecules could lead to new diagnostic tools and therapeutic strategies for this deadly disease.

Keywords: biomarker; circRNAs; extracellular vesicles; gastric cancer; nanoparticles.

FIGURE 1

The biogenesis, release, and content of exosomes. Exosomes are derived from intracellular multivesicular bodies, which are fused to the plasma membrane and then partly degraded by lysosomes and partly released outside the cell to become exosomes. There are three main ways of information transfer between exosomes and target cells. Exosomal membrane proteins interact with target cell membrane proteins to activate intracellular signaling pathways, fuse directly with the target cell membrane, or transmit the genetic information carried directly to the recipient cell. Almost all cell types can secrete exosomes, which also contain a wide range of nucleic acids, proteins and lipids. Their surface markers mainly include CD63, CD81, CD9, Alix, TSG101, and HSP70.

FIGURE 2

The formation, classification and biological functions of exosomal circRNAs. CircRNAs are usually classified into EIciRNAs, EcircRNAs and ciRNAs according to their constituents, which are derived from exons and introns, respectively, and all three are present in pre-mRNA. circRNAs can act as miRNA sponges to regulate the expression of downstream genes. Exosomal circRNAs were transported into the target cells and bind to RNA-binding proteins and regulate parental gene expression. CircRNAs with open reading frames also have the ability to encode polypeptides.

FIGURE 3

Biological functions of exosomal LncRNAs. The subcellular localization of LncRNA determines its biological functions. The exosomal, lncRNA were trasnported into the target cells and induce or repress gene transcription by directing transcription factors (A), controlling splicing of pre-mRNAs (B), mediating chromatin/histone modifications (C), and modifying chromatin structure (D). In the cytoplasm, lncRNAs can regulate mRNA stability (E), act as scaffolds for ribonucleoprotein complexes (F), mediate protein phosphorylation (G), act as miRNA sponges (H), and encode micropeptides (I).