TGF-β-induced acetylation of KLF5 drives TNFAIP2 transcription and EMT in nasopharyngeal carcinoma: Unveiling a novel regulatory mechanism

Abstract

Epithelial-mesenchymal transition (EMT) is one of the critical mechanisms underlying migration, invasion, and metastasis of nasopharyngeal carcinoma (NPC) cells. The transcription factor KLF5 plays a pivotal role in various cancers, however, its precise functions in NPC remain incompletely understood. This study aims to explore the detailed mechanisms by which TGF-β enhances TNFAIP2 transcription by acetylating KLF5, thereby inducing EMT in NPC. KLF5 was significantly overexpressed in NPC tissues and closely associated with adverse clinicopathological features of the patients. Further studies revealed that TGF-β markedly increased the expression of KLF5 and its acetylated form, Ac-KLF5, in NPC cells, with the acetylation status of KLF5 being crucial for its function. KLF5 induced EMT in NPC cells by directly binding to the TNFAIP2 promoter and promoting its transcription. The pro-migratory and pro-invasive effects of acetylated KLF5 on NPC cells depended on TNFAIP2. Additionally, in vivo experiments confirmed that TGF-β treatment induced tumors in NPC mouse models to exhibit apparent EMT characteristics. These results collectively support the central role of the TGF-β-KLF5-TNFAIP2 axis in EMT of NPC. This study elucidates the specific mechanisms by which TGF-β promotes TNFAIP2 transcription by acetylating KLF5, thereby inducing EMT in NPC. This discovery not only provides new insights into the pathogenesis of NPC but also identifies potential therapeutic targets for NPC treatment.