CircUSP1 as a novel marker promotes gastric cancer progression via stabilizing HuR to upregulate USP1 and Vimentin.

ABSTRACT

Circular RNAs (circRNAs) play a crucial role in regulating various tumors. However, their biological functions and mechanisms in gastric cancer (GC) have not been well understood. Here, we discovered a stable cytoplasmic circRNA named circUSP1 (hsa_circ_000613) in GC. CircUSP1 upregulation in GC tissues was correlated with tumor size and differentiation. We observed that circUSP1 promoted GC growth and metastasis. Mechanistically, circUSP1 mainly interacted with the RRM1 domain of an RNA-binding protein (RBP) called HuR, stabilizing its protein level by inhibiting ß-TrCP-mediated ubiquitination degradation. The oncogenic properties of HuR mediated promotive effects of circUSP1 in GC progression. Moreover, we identified USP1 and Vimentin as downstream targets of HuR in post-transcriptional regulation, mediating the effects of circUSP1. The parent gene USP1 also enhanced the viability and mobility of GC cells. Additionally, tissue-derived circUSP1 could serve as an independent prognostic factor for GC, while plasma-derived circUSP1 showed promise as a diagnostic biomarker, outperforming conventional markers including serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA19-9). Our study highlights that circUSP1 promotes GC progression by binding to and stabilizing oncogenic HuR, thereby facilitating the upregulation of USP1 and Vimentin at the post-transcriptional level. These findings suggest that circUSP1 could be a potential therapeutic target and a diagnostic and prognostic biomarker for GC.