Tumor-derived exosomal miR-619-5p promotes tumor angiogenesis and metastasis through the inhibition of RCAN1.4.

Tumor-derived exosomes (TEXs) contain enriched miRNAs that act as novel non-invasive biomarkers for cancer diagnosis and play a role in cancer progression. We investigated the exosomal miRNAs that affect cancer progression in non-small cell lung cancer (NSCLC) and identified the specific molecules involved. We identified that specific miRNAs in NSCLC cell-released exosomes can modulate angiogenesis, among which miR-619-5p was the most potent inducer. RCAN1.4 was identified as a target of miR-619-5p and its suppression promoted angiogenesis. Furthermore, the suppression of RCAN1.4 induced cell proliferation and metastasis in NSCLC cells. In patients with NSCLC, the level of RCAN1.4 expression was significantly lower, and that of miR-619-5p significantly higher, in tumor than normal lung tissues. miR-619-5p expression was higher than normal in exosomes isolated from the plasma of NSCLC patients. Finally, hypoxic conditions induced miR-619-5p upload into NSCLC cell-derived exosomes. Our findings indicate that exosomal miR-619-5p promotes the growth and metastasis of NSCLCs by regulating RCAN1.4 and can serve as a diagnostic indicator for these lung cancers. Tumor-derived exosomes (TEXs) contain enriched miRNAs that act as novel non-invasive biomarkers for cancer diagnosis and play a role in cancer progression. We investigated the exosomal miRNAs that affect cancer progression in non-small cell lung cancer (NSCLC) and identified the specific molecules involved. NSCLC cell-derived exosomal miR-619-5p targets RCAN1.4, and it has a dual function in tumor progression as the promotion of angiogenesis in HUVECs, and proliferation and metastasis in NSCLC cells. In addition, hypoxic conditions induce the secretion of exosomes containing miR-619-5p in certain NSCLC cells. Image 1 • miR-619-5p targets RCAN1.4. • Exosomal miR-619-5p induces angiogenesis in endothelial cells. • Exosomal miR-619-5p promotes cancer proliferation and metastasis in NSCLC cells. • Hypoxia induces miR-619-5p upload into NSCLC cell-derived exosomes. • Exosomal miR-619-5p can serve as a diagnostic indicator for lung cancers. [ABSTRACT FROM AUTHOR]