Mechanism of circ_0075961 promoting invasive metastasis of laryngeal squamous cell carcinoma cells by regulating the EMT process through ZEB1.

Abstract

Laryngeal squamous cell carcinoma (LSCC), the most common subtype of laryngeal cancer, often exhibits poor responsiveness to conventional therapies. Although circRNAs have been implicated in various malignancies, their roles in LSCC remain incompletely understood. This study aimed to investigate the function and underlying mechanism of circ_0075961 in LSCC progression. Expression levels of circ_0075961 and ZEB1 were measured in 32 paired LSCC and ANT tissues using RT-qPCR. Functional assays, including CCK-8, colony formation, and transwell assays, were conducted to assess cell proliferation, migration, and invasion. The interaction between circ_0075961 and ZEB1 was validated by RIP assay. EMT-related protein expression was evaluated by WB. Additionally, a xenograft mouse model was used to verify the role of ZEB1 in vivo. The results showed that circ_0075961 and ZEB1 were significantly upregulated in LSCC tissues and cell lines. Knockdown of circ_0075961 or ZEB1 significantly inhibited the proliferation, migration, and invasion of LSCC cells. Mechanistically, circ_0075961 appeared to regulate these phenotypes by modulating the EMT process through ZEB1. Knockdown of circ_0075961 led to increased E-cadherin and decreased ZEB1, N-cadherin, and Vimentin expression. In vivo, ZEB1 knockdown markedly suppressed tumor growth in a xenograft model. In conclusion, circ_0075961 is associated with malignant phenotypes in LSCC, including tumor cell proliferation, migration, invasion, and EMT, with these effects potentially linked to ZEB1 regulation. These findings suggest that circ_0075961 may serve as a potential therapeutic target and a promising candidate for further exploration as a biomarker, providing new insights into LSCC treatment strategies.