Tumor-Derived Exosomal LINC01480 Upregulates VCAM1 Expression by Acting as a Competitive Endogenous RNA of miR-204-5p to Promote Gastric Cancer Progression

Abstract

Exosomes are a type of cell-derived vesicles that range in size from 30 to 100 nm. They are widely present in various organisms and participate in diverse biological processes, playing crucial roles in tumorigenesis and progression. This study aimed to investigate whether LINC01480 in tumor-derived exosomes is involved in the molecular mechanism of gastric cancer by competitively upregulating the VCAM1 expression through binding miR-204-5p. The study analyzed transcriptome data related to gastric cancer from the cancer genome atlas database and constructed a risk-scoring model for epithelial−mesenchymal transition (EMT)-related lncRNAs to identify eight EMT-related lncRNAs associated with prognosis. EMT-related mRNAs positively correlated with LINC01480 were screened in the ExoRBase database. In vitro cell experiments showed that exosomal LINC01480 can promote the proliferation, migration, invasion, and EMT of gastric cancer cells by upregulating VCAM1 expression through competitive binding with miR-204-5p. In vivo experiments on nude mice showed that exosomal LINC01480 promotes the development of gastric cancer. These results suggest that exosomal LINC01480 could be a potential therapeutic target for gastric cancer.

The biological role of extracellular vesicles in gastric cancer metastasis

“…During EMT, tumor cells lose polarity of epithelial cells and acquire mesenchymal-like motility, which enhances their invasive and migratory abilities, which is considered as the initial stage of tumor metastasis ( Maharati and Moghbeli, 2023 ). EVs can carry various bioactive molecules, including proteins, lipids, and nucleic acids, that can regulate EMT by modulating gene expression, activating related signaling pathways, and altering the TME, thereby influencing the metastatic ability of GC ( Pan et al, 2017 ; Piao et al, 2021 ; Zhang et al, 2023a ; Chen et al, 2023b ). Figure 4 depicts the relevant mechanisms by which EVs modulate EMT to influence GC metastasis.…”

“…Frontiers in Cell and Developmental Biology frontiersin.org including proteins, lipids, and nucleic acids, that can regulate EMT by modulating gene expression, activating related signaling pathways, and altering the TME, thereby influencing the metastatic ability of GC (Pan et al, 2017;Piao et al, 2021;Zhang et al, 2023a;Chen et al, 2023b). Figure 4 depicts the relevant mechanisms by which EVs modulate EMT to influence GC metastasis.…”

“…However, further in vivo experiments are needed to confirm this finding. In addition, the specific molecular mechanisms by which FRLnc1 functions in GC metastasis also need to be further studied (Zhang et al, 2021a). Zhao et al reported that the levels of LINC00355 in plasma EVs of GC patients were significantly higher, when compared with healthy patients, and LINC00355 was found to promote the metastasis of GC cells.…”