Work

CircINADL promotes nasopharyngeal carcinoma metastasis by inhibiting HuR ubiquitin degradation and disrupting the hippo signaling pathway

Year: 2024

Type: article

Abstract: Distant metastasis is a primary factor contributing to the low survival rate of patients with nasopharyngeal carcinoma (NPC). Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer initiation and progression. However, the mechanisms underlying the abnormal expression and biological function of circRNA in NPC remain unclear. In this study, we identified a new circRNA, circINADL, which was upregulated in NPC tissues and positively correlated with the clinical stage of NPC. We found that the FUS RNA binding protein (FUS) promoted the transcription of circINADL in NPC cells. Elevated circINADL levels were shown to enhance NPC cells metastasis. Mechanistically, circINADL attenuated the interaction between human antigen R (HuR) and the E3 ubiquitin ligase β-TrCP, thereby inhibited the ubiquitination and degradation of HuR. Consequently, CircINADL enhanced the stability of the HuR target gene Yes1-associated transcriptional regulator (YAP1), leading to the dysregulation of the Hippo signaling pathway. In conclusion, our study reveals the function of circINADL in promoting NPC metastasis and highlights its potential as a biomarker and therapeutic target for NPC treatment. • circINADL is highly expressed in NPC tissues and cell lines, promoting NPC progression. • FUS regulates the generation of circINADL by binding to its precursor mRNA in NPC. • circINADL interacts with HuR, preventing its ubiquitination and degradation by β-TrCP. • circINADL-HuR-YAP1 axis provides novel biomarkers and therapeutic targets for NPC.

Source: Cellular Signalling

DOI: 10.1016/j.cellsig.2024.111526