ENTPD1-AS1 promotes gastric cancer by activating the WNT signaling pathway through the FTO/WIF1 axis and interaction with SRSF1

Introduction Gastric cancer (GC) remains a major global health burden. Emerging evidence highlights the critical regulatory roles of long noncoding RNAs (lncRNAs) in GC pathogenesis. The purpose of this study was to explore the role and potential regulatory mechanisms of a lncRNA, ENTPD1-AS1, in GC. Material and methods Functional assays (CCK-8, colony formation, wound healing and Transwell assays) were performed in AGS and MKN45 cells following ENTPD1-AS1/SRSF1 knockdown or WIF1 overexpression. Targets were screened via RNA-seq and bioinformatics (UALCAN and SRAMP databases). The m6A modification levels were assessed by MeRIP-qPCR, and molecular interactions were validated by RNA immunoprecipitation (RIP) and immunofluorescence (IF) assays. Results Knockdown of ENTPD1-AS1 & SRSF1 and overexpression of WIF1 inhibited the proliferation, migration, and invasion of GC cells. Inhibition of ENTPD1-AS1 also increased the m6A modification levels in GC cells. Mechanistically, ENTPD1-AS1 downregulated WIF1 through FTO-mediated low levels of m6A modification to promote β-catenin expression, thereby activating the WNT signaling pathway and exacerbating GC. Additionally, ENTPD1-AS1 promoted GC progression by enhancing β-catenin expression through interaction with SRSF1 to activate the WNT signaling pathway. Conclusions In summary, the research highlights the significance of the ENTPD1-AS1/FTO/WIF1 axis and the ENTPD1-AS1/SRSF1 axis in collaboratively activating the WNT signaling pathway. These findings identify ENTPD1-AS1 as a potential therapeutic target for GC.