<i>CircUBAP2(9,12)</i> Inhibits Nasopharyngeal Carcinoma Invasion and Metastasis by Down-regulating <i>ZEB2</i> through Competitive Binding to AUF1

Nasopharyngeal carcinoma (NPC) is identified as a highly aggressive epithelial malignancy. Despite advances in therapy, metastatic relapse remains the leading cause of mortality, underscoring the urgent need for novel molecular targets. Although circular RNAs participate in tumor initiation and progression, their biological functions and internal mechanisms in NPC metastasis remain largely undefined. In this study, we identified a novel circular RNA, <i>circUBAP2(9,12)</i>, generated by back-splicing of exons 9 to 12 of the ubiquitin-associated protein 2 (<i>UBAP2</i>) pre-mRNA. <i>CircUBAP2(9,12)</i> was found to be notably down-regulated in NPC tissues, and its low expression was associated with unfavorable prognosis. Functional assays demonstrated that <i>circUBAP2(9,12)</i> suppresses NPC cell migration and metastasis both in vitro and in vivo. Mechanistically, <i>circUBAP2(9,12)</i> competitively binds to the RNA-binding protein adenylate-uridylate-rich binding factor 1 (AUF1), thereby reducing AUF1's interaction with zinc finger E-box binding homeobox 2 (<i>ZEB2</i>) mRNA. This leads to decreased stability of <i>ZEB2</i> mRNA, inhibition of the epithelial-mesenchymal transition, and consequent suppression of NPC metastasis. Overall, this study reveals a critical role of <i>circUBAP2(9,12)</i> in NPC progression and highlights its potential as a therapeutic target for metastatic NPC.