Hsa_circ_0006232 promotes laryngeal squamous cell cancer progression through FUS-mediated EZH2 stabilization

• Published in: Cell cycle (Georgetown, Tex.) Vol. 20; no. 18; pp. 1799 - 1811
• Main Authors: Wu, Tianyi, Wang, Guangke, Zeng, Xianting, Sun, Zhanwei, Li, Shichao, Wang, Weiwei, Yu, Boyu
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 17-09-2021
• Subjects: Animals; Bronchi - cytology; Carcinogenesis - genetics; Carcinogenesis - metabolism; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Disease Progression; Enhancer of Zeste Homolog 2 Protein - genetics; Enhancer of Zeste Homolog 2 Protein - metabolism; Epithelial Cells - metabolism; Gene Silencing; Hsa_circ_0006232; Humans; invasion; Laryngeal Neoplasms - genetics; Laryngeal Neoplasms - metabolism; Laryngeal Neoplasms - pathology; laryngeal squamous cell cancer; Male; Mice; Mice, Inbred BALB C; Mice, Nude; migration; proliferation; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; Research Paper; RNA, Circular - genetics; RNA, Circular - metabolism; RNA-Binding Protein FUS - genetics; RNA-Binding Protein FUS - metabolism; Signal Transduction - genetics; Squamous Cell Carcinoma of Head and Neck - genetics; Squamous Cell Carcinoma of Head and Neck - metabolism; Squamous Cell Carcinoma of Head and Neck - pathology; Transfection; Tumor Burden - genetics; Xenograft Model Antitumor Assays; Hsa_circ_0006232; migration; laryngeal squamous cell cancer; invasion; proliferation
• ISSN: 1538-4101; 1551-4005
• DOI: 10.1080/15384101.2021.1959973

Laryngeal squamous cell cancer (LSCC) is one of the most common malignant tumors in head and neck tumors. Our previous study has revealed that hsa_circ_0006232 is abnormally expressed in LSCC. This study attempts to verify the biological role of hsa_circ_0006232 in LSCC. We found that compared with human bronchial epithelial cells, hsa_circ_0006232 was highly expressed in human LSCC cells (AMC-HN-8 and TU686). Moreover, hsa_circ_0006232 promoted proliferation, migration and invasion of AMC-HN-8 and TU686 cells. Hsa_circ_0006232 promoted the expression of enhancer of zeste homolog 2 (EZH2) and repressed the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Fused in sarcoma (FUS) interacted with hsa_circ_0006232 and EZH2, and FUS promoted the stabilization of EZH2. Hsa_circ_0006232 inhibited PTEN by promoting FUS expression. Moreover, we constructed a tumor xenograft model by injection of AMC-HN-8 cells with hsa_circ_0006232 knockdown, and we found that hsa_circ_0006232 deficiency decreased tumor growth in mice. Hsa_circ_0006232 silencing repressed EZH2 expression and enhanced PTEN expression in tumor tissues. In conclusion, our data have demonstrated that Hsa_circ_0006232 promotes proliferation, migration and invasion of LSCC cells, and accelerates tumor growth of LSCC through FUS-mediated EZH2 stabilization. Thus, hsa_circ_0006232 may be a novel therapeutic target in LSCC treatment.