Circ_0008777 promotes head and neck squamous cell carcinoma progression by elevating c-Myc expression levels via interacting with PC4 and miR-185–3p

Circular RNAs (circRNAs) have emerged as key players in tumor progression, yet their role in head and neck squamous cell carcinoma (HNSCC) remains largely unexplored. The AURKA gene is frequently amplified and activated in HNSCC. This study investigates the expression patterns and functions of circ_0008777, which is derived from AURKA exons 3-6, in HNSCC. The biological functions of circ_0008777 were evaluated in vitro and in vivo, along with its interactions with positive cofactor 4 (PC4) and miR-185-3p. Our data indicated that circ_0008777 expression levels are upregulated in HNSCC tissues and cell lines, and linked to aggressive clinical features. Knocking down circ_0008777 significantly inhibited HNSCC cell proliferation and migration in vitro, as well as restrained tumor growth in vivo, while overexpressing circ_0008777 had the opposite effects. Mechanistically, circ_0008777 can bind to PC4 to increase c-Myc transcription. Bioinformatics analysis showed that PC4 is highly expressed in HNSCC patients, with survival analysis revealing a negative correlation between PC4 expression and overall survival rates. PC4 knockout could hinder HNSCC cell proliferation and migration in vitro. Additionally, circ_0008777 can bind to miR-185-3p through a microRNA sponge mechanism, relieving miR-185-3p-mediated repression of c-Myc mRNA. Furthermore, the inhibitory effects of circ_0008777 knockdown on the cell migration and proliferation rates were rescued by c-Myc overexpression. In conclusion, circ_0008777 can promote HNSCC progression by upregulating c-Myc expression through both PC4- and miR-185-3p-related mechanisms, showing potential as a candidate therapeutic target in this cancer.