Exosomal circ_0008803 drives lung cancer cell migration and invasion via NF-κB activation

Abstract

Exosomes facilitate intercellular communication and play a critical role in tumor development. Circular RNA (circRNA), a major component of exosomes, is involved in cancer metastasis through exosome-mediated delivery. This study identified a novel non-small-cell lung cancer (NSCLC)-associated circRNA, circ_0008803 in exosomes. We found that circ_0008803 promoted the migration and invasion of NSCLC cells in vitro and facilitated tumor growth in vivo. Using confocal microscopy, we observed that circ_0008803 was encapsulated in exosomes and transported to recipient cells. Upon release into recipient cells, circ_0008803 competitively bound to miR-432-5p, which upregulated the expression of transformer 2 beta homolog (TRA2B). Concurrently, circ_0008803 interacted with the ELAV-like RNA-binding protein 1 (ELAVL1) and promoted the translocation of ELAVL1 from the nucleus to the cytoplasm. The circ_0008803-ELAVL1 complex further interacted with the 3’untranslated region (3’UTR) of TRA2B, enhancing the stability of TRA2B in the cytoplasm. Through these mechanisms, the upregulated TRA2B activated the NF-κB pathway, thereby promoting the migration and invasion of recipient cells. Furthermore, elevated serum exosomal circ_0008803 levels correlated with advanced NSCLC stages and distant metastasis. In summary, this study highlights circ_0008803 as a novel exosomal circRNA implicated in NSCLC metastasis, providing mechanistic insights and underscoring its potential as a diagnostic biomarker.