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neo_2020_190411N321

Title: Effect of GATA4 gene methylation on proliferation and apoptosis of SGC-7901 gastric cancer cells
Author: X. MA, L. JI

Abstract: Gastric cancer (GC) remains a major cause of cancer-related deaths worldwide. GATA4 has been previously reported to exhibit functions in GC. In this study, we aimed to investigate effect of GATA4 gene methylation on GC progression. Methylation-Sensitive High-Resolution Melting was used to detect the methylation of GATA4 promoter region in GC tissues and adjacent normal tissues, GC cell lines and GES-1 cells. The relationship between GATA4 methylation level and clinical characteristics of GC patients was analyzed. GATA4 levels in GC tissues and adjacent normal tissues, GC cell lines and GES-1 cell lines were detected, and gain-of function was performed to investigate the role of GATA4 in GC. Si-GATA4 was transfected into GES-1 cells to observe the changes of various indicators. RNA-seq detected the differentially expressed genes in SGC-7901 cells overexpressing GATA4, and western blot analysis verified their expression. GATA4 methylation rate was increased in GC tissues, and GATA4 promoter was abnormally methylated in GC cells. GATA4 methylation rate in GC tissues was related to lymph node metastasis, differentiation degree and clinical stage of GC patients. Lower expressed GATA4 was observed in GC tissues and cells. Cell proliferation rate decreased and cell apoptosis rate increased in SGC-7901 cells overexpressing GATA4. Transfecting si-GATA4 into GES-1 cells led to increased proliferation, inhibited apoptosis, and restoration of GATA4 led to decreased APC and GSK3β levels. In conclusion, restoration of GATA4 caused by 5-Aza treatment can inhibit the proliferation and promote apoptosis of GC cells possibly via Wnt/β-catenin signaling pathway. This study may offer new sight for GC treatment.

Keywords: Gastric cancer; GATA4; Promoter methylation; Proliferation; Apoptosis
Published online: 16-Apr-2020
Year: , Volume: , Issue: Page From: , Page To:
doi:10.4149/neo_2020_190411N321


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