MALAT1 Promotes Tumor Growth And Metastasis Via VHL/β-catenin Pathway In Oral Squamous Cell Carcinoma

Objective Metastasis associated lung adenocarcinoma transcript 1(MALAT1)is one of the earliest discovered long non-coding RNA.Many studies have shown that MALAT1 plays an important role in many diseases,especially in the development and progression of malignant tumors.MALAT1 shows an abnormal expression in many human malignancies such as esophageal cancer,glioma,renal cell carcinoma.,and MALAT1 is a prognostic factor.Our previous study has found that high level of MALAT1 is related to poor prognosis in oral squamous cell carcinoma(OSCC).It is suggested that MALAT1 may be involved in malignant progression of OSCC.Our study aims to investigate the effects of MALAT1 on proliferation,apoptosis,migration and invasion of OSCC and its possible mechanism.Methods 1.Collect 69 cases of OSCC tissues and each of them was immunohistochemical stained.Analysis of the relationship between beta-catenin protein and VHL protein in oral squamous cell carcinoma with gender,age,tumor location,T stage,histological differentiation and lymph nodes metastasis.Analysis the correlation relationship between the expression of VHL and beta-catenin protein.2.Our study chose UM1 and SCC25 cell carcinoma cell lines to transfected MALAT1-si RNA.We used CCK8 and colony formation assay to detect the effects of MALAT1 on cell proliferation,flow cytometry to detect the change of cell cycle and cell apoptosis.Cell migration and invasive ability were evaluated by Transwell assay and cell migration assay.The expression of proteins that regulated cell cycle,apoptosis,EMT,invasion and migration and VHL,β-catenin were examined using Western blot assay.Results 1.The immunohistochemical stain of 69 cases showed that low expression of VHL is related to poor histological differentiation and lymph node metastasis,and there was no relationship between VHL with gender,age,tumor location and T stage.High expression of beta-catenin is related to lymph node metastasis but there was no relationship between beta-catenin with gender,age,tumor location,T stage and histological differentiation.The expression of VHL was negatively correlated with the expression of beta-catenin.2.After MALAT1 expression was down-regulated in OSCC cells,the number of colony was reduced,proliferation was inhibited,the number of cells in G0/G1 stage was decreased and the number of cells in S stage was increased,G1/S arrest was triggered.Expression of Cyclin D1 was downregulated and p21 was upregulated.Cell apoptosis was increased and expression of Bax and cleaved caspase-3 were upregulated.Migration and invasion were attenuated and expression of N-cadherin,Vimentin and MMP-2/9 were downregulated and the expression of E-cadherin were upregulated in the cells after MALAT1 was knocked down,showing significant differences compared with the cells transfected with negative control cells.In the meanwhile,we found that expression of VHL was upregulated and β-catenin was downregulated.Conclusion 1.In OSCC,the expression of VHL is related to histological differentiation and lymph node metastasis.The expression of beta-catenin is related to lymph node metastasis.The expression of VHL is negatively correlated with the expression of beta-catenin.2.MALAT1 can promote growth and proliferation and inhibit apoptosis of tumor cells in OSCC.MALAT1 can also promote the migration and invasion of OSCC cells by inducing EMT process.3.MALAT1 may modulates the growth and invasion in OSCC through VHL/β-catenin signaling pathway.