Abstract
Gastric cancer (GC) is a common cancer and a leading cause of cancer-related deaths worldwide. Recent studies have supported the important role of long non-coding RNAs (lncRNAs) in GC progression. This study identified functional significance of X inactive specific transcript (XIST) in GC. The expression of XIST and EPHA1 in GC tissues and cells was measured. Then, dual luciferase reporter gene assay, RNA immunoprecipitation (RIP) assay and Chromatin Immunoprecipitation (ChIP) assay were performed to explore the interaction among XIST, EPHA1 and HNF4A. The effects of XIST on GG progression were evaluated by determining expression of proliferation- and invasion-related proteins (Ki67, PCNA, MMP-2, and MMP-9). Further, the functional role of XIST in GC with the involvement of NFκB pathway was also analyzed. Subsequently, the tumor growth in nude mice was evaluated. High expression of XIST and EPHA1 was observed in GC. XIST elevated EPHA1 expression by recruiting HNF4A. In addition, silencing of XIST inhibited GC progression in vitro and in vivo. Overexpressed XIST and EPHA1 yielded a reversed effect on cell proliferation and invasion. SN50 treatment (inhibitor of NFκB pathway) counteracted the promotive effect on GC cell proliferation and invasion mediated by XIST. The present study unveils that XIST increases the enrichment of HNF4A in the promoter region of EPHA1, thus promoting the deterioration of GC.