Reprogramming of hsa_circ_0008719 and its target miR-3615 induced by TOB1 in exosomes of gastric cancer cells: a contribution to inhibit gastric cancer progression.

Circular RNAs (circRNAs) are highly stable and abundant in tumor-derived exosomes, where they often function as microRNA (miRNA) sponges to regulate gene expression and biological processes. Previous research showed that Transducer of ERBB2.1 (TOB1) overexpression induces autophagy and suppresses gastric cancer progression through exosome secretion. This study investigates the relationship between TOB1, exosomal circRNAs, and their target miRNAs in gastric cancer. RNA sequencing and bioinformatics analyses identified differentially expressed circRNAs and miRNAs in exosomes from gastric cancer cells. qRT-PCR revealed that hsa_circ_0008719 was downregulated in gastric cancer tissues compared to normal tissues. Further analysis showed that TOB1 upregulates hsa_circ_0008719 and downregulates miR-3615 in gastric cancer cells and their exosomes. Functional assays, including lentiviral infection, Cell Counting Kit-8 (CCK-8), colony formation, and Western blot, demonstrated that exosomal hsa_circ_0008719 inhibits proliferation and promotes autophagy in gastric cancer cells. Differential expression analysis identified 87 upregulated circRNAs and 1 upregulated miRNA, as well as 2 downregulated circRNAs and 8 downregulated miRNAs in exosomes from TOB1-overexpressing AGS cells. Twelve novel circRNAs were discovered. GO and KEGG analyses linked the host gene of hsa_circ_0008719, AKT2, to gastric cancer and autophagy pathways. hsa_circ_0008719 was found to localize in the cytoplasm, where it binds to miR-3615. These findings highlight the TOB1-hsa_circ_0008719-miR-3615 axis in gastric cancer, showing that exosomal hsa_circ_0008719 suppresses cancer progression by enhancing autophagy and reducing proliferation. This study provides insights into the role of TOB1-mediated exosomal circRNAs in gastric cancer regulation.