Effect Of Long Non-coding RNA CCAT2 On The Biological Behavior Of Oral Squamous Cell Carcinoma And Mechanism Exploration

Objective: Oral squamous cell carcinoma(OSCC)is one of the most common tumors in head and neck,which characterized with high malignancy,prone to local invasion and cervical lymph node metastasis.The carcinogenesis of OSCC is a multi gene and variety factors participates process.Of note,long non-coding RNAs(lnc RNAs)were reported to be a class of most researched regulators.Colon cancer-associated transcript2(CCAT2),belongs to lnc RNAs,locates in 8q24.21 has been reported to be consistently abnormal expression in colorectal cancer,lung cancer and renal carcinoma,and the expression level of CCAT2 in these cancers is closely related to its clinical pathologic grade and prognosis.Meantime,the CCAT2 contributed to the progression and metastasis of colon cancer by mediating the transcription process.Methods:Microarray together with qRT-PCR were used to screen and identify the expression level of CCAT2 in both OSCC tissues and cells.Meanwhile,its relationship with clinical characteristics was analyzed by the Kaplan-Meier survival curve.The biological behaviors of CCAT2 in oral squamous cell carcinoma were explored by the use of CCAT2 knockdown and cell transfection technologies.TOP/FOP Flash luciferase reporter assay was used to detect the activity of Wnt/ ?-catenin signal pathway.The Wnt/ ?-catenin pathway agonist lithium chloride(Li Cl)was used to further explore the mechanism of CCAT2 mediated biological behavior alteration.Results: Microarray together qRT-PCR results revealed that CCAT2 was up-regulated in both 62 clinical tumor samples and 2 OSCC cell lines compared with corresponding controls.Kaplan Meier survival analysis and log-rank test discovered that patients with CCAT2 high-expression level was correlated with poor differentiation,higher T stage and M stage,and has no influence on N stage,patient's age,gender,smoking,drinking alcohol and position.The higher the expression of CCAT2,the lower the survival rate of OSCC patients.Silence CCAT2 expression can significantly inhibit the proliferation and invasion abilities and promote the apoptosis rate of OSCC TCA8113 and CAL27 cells.Meanwhile,knockdown CCAT2 of OSCC cells can suppress ?-catenin expression,reduce the transcription activity of Wnt/?-catenin signal pathway and its target genes CCND1 and MYC expression in OSCC cells.Li Cl activated the Wnt/?-catenin signal pathway could activate CCND1,MYC and suppress glycogen synthase kinase-3 ?(GSK-3 ?)expression and partly restore the CCAT2 mediated malignant biological behaviors of OSCC cells.Conclusion: CCAT2 functioning as a potential oncogene was up-regulated in OSCC.CCAT2 with high-expression level was correlated with poor differentiation,higher T stage and clinical stage,which made CCAT2 to be a prognostic biomarker in OSCC.Li Cl activated the Wnt/ ?-catenin signal pathway could partly restore the CCAT2 mediated malignant biological behaviors of OSCC cells by suppressing ?-catenin,CCND1,MYC and activating glycogen synthase kinase-3 ?(GSK-3?)expression.