Exosomal LncRNAs in Gastrointestinal Cancer: Biological Functions and Emerging Clinical Applications

Abstract

Due to the lack of specific and effective biomarkers and therapeutic targets, the early diagnosis and treatment of gastrointestinal cancer remain unsatisfactory. As a type of nanosized vesicles derived from living cells, exosomes mediate cell-to-cell communication by transporting bioactive molecules, thus participating in the regulation of many pathophysiological processes. Recent evidence has revealed that several long non-coding RNAs (lncRNAs) are enriched in exosomes. Exosomes-mediated lncRNAs delivery is critically involved in various aspects of gastrointestinal cancer progression, such as tumor proliferation, metastasis, angiogenesis, stemness, immune microenvironment, and drug resistance. Exosomal lncRNAs represent promising candidates to act as the diagnosis biomarkers and anti-tumor targets. This review introduces the major characteristics of exosomes and lncRNAs and describes the biological functions of exosomal lncRNAs in gastrointestinal cancer development. The preclinical studies on using exosomal lncRNAs to monitor and treat gastrointestinal cancer are also discussed, and the opportunities and challenges for translating them into clinical practice are evaluated.

Unraveling the Intricate Roles of Exosomes in Cardiovascular Diseases: A Comprehensive Review of Physiological Significance and Pathological Implications

“…In recent years, the study of exosomes as important mediators of cell communication has emerged endlessly [88,89]. Exosomes facilitate communication with recipient cells through various mechanisms, including ligand binding directly to the receptor to activate downstream signaling, direct membrane fusion resulting in the release of exosome contents into the recipient cells, and internalization of exosomes by the recipient cells through endocytosis (including phagocytosis, macrophage, or receptor-mediated endocytosis) [90].…”

Tumor Microenvironment Modulation by Cancer-Derived Extracellular Vesicles

“…When determining the mechanism of action, it was proposed that hsa_circ_0000069 acts as a sponge for miR-144 by increasing the expression of the STIL gene by the main regulator of the mitotic centrosome [56]. In addition to circulating RNAs, it has been shown that gastric cancer cells secrete exosome-packaged long noncoding RNA (lncRNA) SND1-IT1 [57]. Internalization of this lncRNA by human gastric mucosa epithelial GES-1 cells caused cell malignant transformation by enhancing the expression of ubiquitin-specific protease 3 (USP3), inhibiting miR-1245b-5p, and simultaneously recruiting DEAD-box helicase 54 (DDX54).…”

The landscape of lncRNAs in gastric cancer: from molecular mechanisms to potential clinical applications

“…The stability can be explained by their packing in extracellular vesicles such as apoptotic bodies, microvesicles, and exosomes. Circulating exosomal lncRNAs have emerged as promising biomarkers for GC ( Zhang et al, 2021 ; Badowski et al, 2022 ; Sun et al, 2023 ).…”

“…In GC, these transcripts play a crucial role in promoting carcinogenesis through the modulation of cellular mechanisms, such as proliferation, stemness, tumor immune escape, invasion, angiogenesis, and drug resistance of tumor cells ( Zhang X.-Z. et al, 2020 ; Gui et al, 2021 ; Jiang et al, 2021 ; Razavi et al, 2021 ; Sun et al, 2023 ).…”