Exosomal miR-552-5p promotes tumorigenesis and disease progression via the PTEN/TOB1 axis in gastric cancer

Purpose Gastric cancer (GC) is associated with rapid disease progression and poor patient prognosis, highlighting the pressing need for new biomarkers to facilitate disease management. Exosomes are released by all cells and are ubiquitous in body fluids, thus giving them great potential as diagnostic biomarkers and therapeutic targets. MicroRNAs (miRNAs) can be transported by exosomes, and are a common target for regulation in cancer. Methods Our screen of miRNAs in the Gene Expression Omnibus and The Cancer Genome Atlas databases identified miR-552-5p as the most overexpressed miRNA in GC, and we investigated its function and mechanism of action. Results We detected high expression of miR-552-5p in GC tissues, plasma samples and cell lines. We found that miR-552-5p binds directly to the 3'-untranslated region of PTEN, and the resulting downregulation of PTEN in turn downregulates the tumor suppressor TOB1. Furthermore, experiments in cell culture and mice showed that miR-552-5p in exosomes is internalized by recipient cells, where it enhances proliferation, migration and the epithelial-mesenchymal transition, while suppressing the caspase-3 apoptotic pathway. These effects were reversed by inhibiting miR-552-5p. Conclusion GC-derived exosomal miR-552-5p facilitates tumorigenesis by interfering with the PTEN/TOB1 axis, providing new potential therapeutic targets.

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