SEPT9_v2, frequently silenced by promoter hypermethylation, exerts anti-tumor functions through inactivation of Wnt/β-catenin signaling pathway via miR92b-3p/FZD10 in nasopharyngeal carcinoma cells
Yu Jiang, Lei Liu, Xiang Qin, Xiaoqian He, Yan Wang, Dishu Zhou, Can Zou, Qian Chen, Mingyu Peng, Jin He, Xianyao Jiang, Tingxiu Xiang, Yucheng Yang
Abstract
BACKGROUND: Nasopharyngeal carcinoma tends to present at an advanced stage because the primary anatomic site is located in a less visible area and its clinical symptoms are nonspecific. Prognosis of advanced nasopharyngeal carcinoma cases remains disappointing. SEPT9 is a methylation-based biomarker approved by the US Food and Drug Administration for colorectal cancer screening and diagnosis. Interestingly, downregulation of SEPT9, especially SEPT9_v2, mediated by promoter hypermethylation has been also detected in head and neck squamous cell carcinoma than in head and neck squamous epithelium, while other SEPT9 variants did not. These reasons above indicate a crucial role of SEPT9_v2 in cancer progression. Therefore, we address the methylation status of SEPT9_v2 in nasopharyngeal carcinoma and explore the role of SEPT9_v2 in nasopharyngeal carcinoma proliferation and cancer progression. RESULTS: SEPT9_v2 expression was found to be downregulated via promoter methylation in nasopharyngeal carcinoma cell lines and tissues. Ectopic expression of SEPT9_v2 induced G0/G1 cell cycle arrest and apoptosis, which exerted an inhibitory effect in cell proliferation and colony formation. Additionally, nasopharyngeal carcinoma cell migration and invasion were shown to be inhibited by SEPT9_v2. Furthermore, our data suggested that SEPT9_v2 inhibits proliferation and migration of nasopharyngeal carcinoma cells through inactivation of the Wnt/β-catenin signaling pathway via miR92b-3p/FZD10. CONCLUSIONS: This study delineates SEPT9_v2, frequently silenced by promoter hypermethylation, exerts anti-tumor functions through inactivation of the Wnt/β-catenin signaling pathway via miR92b-3p/FZD10 in nasopharyngeal carcinoma cells and, hence, SEPT9_v2 may be a promising therapeutic target and biomarker for nasopharyngeal carcinoma.