Function And Methylation Status Of LATS1 In Esophageal Squamous Cell Carcinoma

Background:Large tumor suppressor kinase 1(LATS1)is a key element in the Hippo signaling pathway and was identified as a tumor suppressor gene.Deactivation of LATS1 by hypermethylation of CpG islands were detected in several cancers.But,how the methylation of LATS1 CpG islands affects expression and cell ability has not been studied in esophageal squamous cell carcinoma.Objective:To investigate the relationship between LATS1 gene expression and methylation status of LATS1 promoter in esophageal squamous cell carcinoma(ESCC).And explore its role in the development and progression of carcinoma and the possibility of LATS1 as a target of gene therapy for ESCC.Methods:1.LATS1 expression in ESCC was detected by qRT-PCR and immunohistochemical staining.The relationship between LATS1 and clinicopathological features and staging was also discussed.2.Methylation status of LATS1 CpG islands in ESCC tissues and celss was detected by Methylation-specific PCR and bis?lfite genomic sequencing.3.Esophageal squamous cell carcinoma cell line TE-10 and EC109 was chosen to overexpress LATS1 gene by lentivirus.4.The effect of LATS1 gene on the proliferation of TE-10 and EC109 cells was studied by CCK-8 and clone formation assay.5.The effect of LATS1 gene on cell cycle and apoptosis of TE-10 and EC109 cells was detected by flow cytometry.6.The effect of LATS1 gene on the migration and invasion of TE-10 and EC109 cells was examined by transwell assay.7.Data were analyzed using SPSS23.0.Res?lts:1.Expression of LATS1 was downreg?lated in ESCC tissues compared with matched normal tissues located adjacent to ESCC.2.Exogenous expression of LATS1 in ESCC cells obviously inhibited cell proliferation,cell migration and invasion,arrested cell cycle at the G2/M phase and promoted cell apoptosis.3.The methylation site was not found in the CpG island of LATS1 promoter.Conclusions:Our research strongly indicated that LATS1 is a tumor suppressor gene in ESCC and is associated with the clinical stage of the tumor while its downreg?lation has no connection with the hypermethylation of CpG islands.Ectopic expression of LATS1 in ESCC cells evidently inhibited cell proliferation,cell migration and invasion,arrested cell cycle at G2/M phase and promoted cell apoptosis.Thus,it wo?ld be of benefit to further explore the possible uses of LATS1 as a biomarker and a target for future molec?lar therapy and diagnosis.