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

OBJECTIVEMany reports indicate a crucial role of SEPT9_v2 in cancer progress.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.METHODSSemi-quantitative polymerase chain reaction(PCR),quantitative PCR,and methylation specific PCR were used to detect mRNA expression and promoter methylation levels of SEPT9-v2 in nasopharyngeal carcinoma(NPC).Cell proliferation,colony formation,flow cytometric analysis,wound healing,and transwell assays were used to determine the functional effects of SEPT9-v2 on NPC.RNA-seq was used to explore the target genes modulated by SEPT9-v2.Western blot,immunofluorescence,and dual-luciferase reporter assays were used to assess SEPT9-v2 mediated outcomes.RESULTSSEPT9_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,which exerted 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_v2inhibits proliferation and migration of nasopharyngeal carcinoma cells through inactivation of the Wnt/β-catenin signaling pathway via miR92b-3p/FZD10CONCLUSIONSThis study delineates 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 and hence,SEPT9_v2 may be a promising therapeutic target and biomarker for nasopharyngeal carcinoma.