CircHMGA2 facilitates proliferation and invasion of laryngeal squamous cell carcinoma cells and M2 macrophage polarization via the miR-384/ROCK1 axis.

INTRODUCTION: Laryngeal squamous cell carcinoma (LSCC) is a malignant tumor of the head and neck. CircRNA High Mobility Group AT-hook 2 (circHMGA2) has cancer-promoting functions. Nevertheless, the role of circHMGA2 in LSCC has not been reported yet. We attempted to illustrate the function and mechanism of circHMGA2 in LSCC. MATERIAL AND METHODS: The clinicopathological association between circHMGA2 and LSCC was assessed via the chi-square test. The correlation between circHMGA2 and LSCC patient survival time was determined with Kaplan-Meier analysis. Quantitative real-time PCR was applied to determine circHMGA2 expression in LSCC. Cell Counting Kit-8 assay, Western blot, cell invasion, enzyme-linked immunosorbent assay, and co-culture assays were conducted to evaluate circHMGA2 function in LSCC. Dual-luciferase reporter assay and RNA pull-down were performed to explore the role of circHMGA2 in LSCC. Meanwhile, circHMGA2 function in vivo was evaluated using tumor xenograft experiments, hematoxylin-eosin staining, and immunohistochemical assays. RESULTS: CircHMGA2 was raised in LSCC, and elevated circHMGA2 expression was associated with TNM stage of LSCC patients. Patients with elevated circHMGA2 levels had shorter overall survival. Functionally, circHMGA2 knockdown suppressed LSCC cell proliferation and invasion. Also, circHMGA2 knockdown inhibited M2 macrophage polarization. Mechanistically, circHMGA2 targeted miR-384, and miR-384 targeted ROCK1. Also, ROCK1 level was negatively associated with miR-384 in LSCC tissues, but positively associated with circHMGA2. Moreover, rescue experiments suggested that circHMGA2 knockdown ameliorated LSCC growth via miR-384/ROCK1 and suppressed M2 macrophage polarization through miR-384/ROCK1. Meanwhile, circHMGA2 knockdown inhibited LSCC growth in vivo. CONCLUSIONS: CircHMGA2 acts as a competing endogenous RNA, promoting LSCC progression through the miR-384/ROCK1 axis.