Overexpressed long non-coding RNA GATA6-AS1 inhibits lymph node metastasis and epithelial mesenchymal transition via FZD4 through the Wnt/β-catenin signaling pathway in gastric cancer

Abstract Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. Accumulating evidence reveals the significance of long non-coding RNAs (lncRNAs) in various cancers. The current study aimed to evaluate the role of GATA6 antisense RNA 1 (GATA6-AS1) in epithelial mesenchymal transition (EMT) and lymph node metastasis (LNM) in GC. GC-related microarray datasets were initially retrieved from Gene Expression Omnibus with differentially expressed lncRNAs screened, followed by evaluation of regulatory relationship between Frizzled 4 (FZD4) and GATA6-AS1. The detailed regulatory mechanism by which GATA6-AS1 influences the Wnt/β-catenin signaling pathway and GC cell biological behaviors was investigated by treating SGC7901 cells with overexpressed GATA6-AS1, specific antisense oligonucleotide against GATA6-AS1 and LiCl (activator of Wnt/β-catenin signaling pathway). Finally, xenograft nude mice were used to assay tumor growth and LNM in vivo. GATA6-AS1 was poorly expressed, but FZD4 was highly expressed in GC tissues and cells. Elevated GATA6-AS1 reduced FZD4 expression by recruiting EZH2 and H3K27me3 to the FZD4 promoter region via inactivated Wnt/β-catenin signaling pathway, whereby cell invasion, migration and proliferation, tumor growth and LNM in nude mice were reduced. Taken together, overexpressed GATA6-AS1 down-regulated the expression of FZD4 to inactivate the Wnt/β-catenin signaling pathway, which ultimately inhibited GC progression.