IDDF2021-ABS-0076 lncRNA TNFRSF10A-AS1 mediates tumorigenesis of gastric cancer by directly binding to MPZL1 and associates with patient outcomes

Abstract

<h3>Background</h3> LncRNA was known to be closely associated with the progression of human tumors. The role of new lncRNA TNFRSF10A-AS1 in the pathogenesis and progression of gastric tumor is still unclear. The aim of this study was to investigate the function of TNFRSF10A-AS1 and the underlying mechanism in the pathogenesis and progression of gastric cancer. <h3>Methods</h3> The clinical impact of TNFRSF10A-AS1 was assessed in 105 patients with gastric cancer. The biological function of TNFRSF10A-AS1 was studied in vitro and in vivo. TNFRSF10A-AS1 downstream effector were identified by RNA FISH, RNA sequencing, RNA pulldown and rescue assay. <h3>Results</h3> TNFRSF10A-AS1was upregulated in gastric cancer cell lines and tissues. Multivariate analysis showed that gastric cancer patients with TNFRSF10A-AS1 overexpression had a significantly shortened survival. TNFRSF10A-AS1 significantly promoted gastric cancer cell proliferation, cell-cycle transformation, and migration/invasion, but suppressed cell apoptosis. Silencing TNFRSF10A-AS1 expression exerted opposite effects in vitro and significantly inhibited xenograft tumor growth in nude mice. Mechanically, TNFRSF10A-AS1 directly bound to MPZL1 and activated MPZL1 transcription. Knockdown MPZL1 abrogated the effect of TNFRSF10A-AS1 in the tumor-promoting function. <h3>Conclusions</h3> TNFRSF10A-AS1 directly binds to oncogenic MPZL1 to induce its expression. TNFRSF10A-AS1 plays a pivotal oncogenic role in gastric carcinogenesis and is an independent prognostic factor for gastric cancer patients.