circADARB1 enhances ZEB1 expression in an m6A-dependent manner to promote the invasion and migration of nasopharyngeal carcinoma

作者：Dan Wang, J. Mendoza, Pingjuan Xiang, Yi Zhang, Le Tang, Jiarong Zhang, Chunmei Fan, Hongke Qu, Yumin Wang, Zhouying Peng, Ming Zhou, Bo Xiang, Can Guo, Wei Xiong, Lei Shi, Pan Chen, Zhaoyang Zeng · 发表于：International Journal of Biological Macromolecules · 年份：2025 · DOI：10.1016/j.ijbiomac.2025.145187 · 被引用次数：4 · 研究领域：RNA modifications and cancer、Circular RNAs in diseases、Peptidase Inhibition and Analysis

Nasopharyngeal carcinoma (NPC) is an aggressive head and neck malignancy, with invasion and metastasis as the primary drivers of poor prognosis. Although various molecular mechanisms underlying NPC invasion and metastasis have been reported, the overall regulatory network remains unclear, particularly the role of circRNA-mediated regulation, which has not been systematically investigated. In this study, we identified circular RNA circADARB1 as a key regulator of epithelial-mesenchymal transition (EMT) in NPC. We found that circADARB1 binds to the 3’ UTR of ZEB1 mRNA, a transcription factor crucial for EMT, enhancing its stability and promoting EMT, ultimately leading to invasion and metastasis in NPC cells. Furthermore, our results revealed that m 6 A modification of ZEB1 mRNA is essential for circADARB1-mediated stability enhancement. Using RNA pull-down and mass spectrometry, we discovered that circADARB1 facilitates the interaction of YBX1 protein with m 6 A-modified ZEB1 mRNA, thereby stabilizing ZEB1 mRNA and upregulating ZEB1 expression. This study uncovers a novel role of circADARB1 in NPC progression and identifies YBX1 as a potential m 6 A reader, offering new potential molecular markers and therapeutic targets for NPC.