Study Of Mechanisms And Clinical Significance Of The Tumor Suppressor LINC00261 Regulates Invasion And Metastasis Of Laryngeal Squamous Cell Carcinoma Via The MiR-9-3p/CPEB3 Axis

Objective:Studies have shown that long noncoding RNA(LncRNA)plays a key role in tumorigenesis and development,but the molecular regulatory mechanism and corresponding clinical significance of LncRNA in laryngeal squamous cell carcinoma is still unclear.The purpose of this study was to elucidate the molecular regulatory mechanism of tumor suppressor gene LINC00261 in promoting the invasion and metastasis of laryngeal squamous cell carcinoma and its clinical significance.Methods:Analysis of the expression of LINC00261 in laryngeal Squamous cell carcinoma and adjacent tissues and its relationship with clinicopathological parameters by whole transcriptome sequencing.The function of LINC00261 was detected by CCK8,clone formation,flow cytometry,and Transwell(migration and invasion)in vitro.Ectopic xenograft tumor model evaluated the effect of LINC00261 on tumorigenicity of laryngeal Squamous cell carcinoma cells in nude mice.The LINC00261-centered competing endogenous RNA(ceRNA)regulatory network in laryngeal squamous cell carcinoma was constructed by bioinformatics methods.Kaplan-Meier method survival analysis determined key prognostic genes in ceRNA network.Univariate and multivariate regression analysis were used to further construct a cox prognosis model based on the ceRNA network.Double luciferase reporter analysis and rescue experiments verified the LINC00261-miR-9-3p-CPEB3 axis.Results: LINC00261 was down-regulated in laryngeal carcinoma tissues and negatively correlated with pathological parameters such as T stage,clinical stage and lymph node metastasis.LINC00261 inhibited the proliferation,clonal formation,migration and invasion of laryngeal carcinoma cells in vitro and the tumorigenic ability of laryngeal carcinoma cells in vivo.The ceRNA regulatory network centered on LINC00261 in laryngeal carcinoma includes 4 miRNA nodes and 36 mRNA nodes,4 of which are related to patient survival.Univariate and multivariate regression analysis showed that CPEB3,FXYD1 and ENDOU were key prognostic factors,and the cox prognostic model was as follow: riskscore = CPEB3*(-0.456)+ FXYD1*(-0.169)+ ENODU*(-0.0674).In addition,we further confirmed that LINC00261 as a ceRNA adsorbed miR-9-3p to up-regulate CPEB3,a key prognostic factor for laryngeal Squamous cell carcinoma,thereby inhibiting the migration and invasion of laryngeal Squamous cell carcinoma cells.Conclusion: LINC00261 is a tumor suppressor gene in laryngeal Squamous cell carcinoma,and down-regulated LINC00261 as an endogenous competitive RNA up-regulates miR-9-3p to inhibit the expression of the key prognosis factor CPEB3 of laryngeal Squamous cell carcinoma,thereby promoting the migration and invasion of laryngeal Squamous cell carcinoma.Therefore,LINC00261 may be a potential prognostic biomarker for laryngeal Squamous cell carcinoma.