LncRNA TNFRSF10A-AS1 promotes gastric cancer by directly binding to oncogenic MPZL1 and is associated with patient outcome

Background: LncRNA is closely associated with the progression of human tumors. The role of lncRNA TNFRSF10A-AS1 (T-AS1) in gastric cancer (GC) is still unclear. We aim to investigate the functional significance and the underlying mechanisms of T-AS1 in the pathogenesis and progression of GC. Experimental Design: The clinical impact of T-AS1 was assessed in 103 patients with GC. The biological function of T-AS1 was studied in vitro and in vivo. T-AS1 downstream effector were identified by RNA sequencing and RNA pulldown assay. Results: T-AS1 was upregulated in GC cell lines and GC tissues as compared to adjacent non-cancer tissues (n = 47, P < 0.001). Multivariate analysis showed that GC patients with T-AS1 high expression had a significantly shortened survival (n=103, P < 0.05). T-AS1 significantly promoted GC cell proliferation, cell-cycle progression, and cell migration/invasion abilities, but suppressed cell apoptosis. Silencing of T-AS1 in GC cells exerted opposite effects in vitro. Knockout of T-AS1 significantly inhibited xenograft tumor growth in nude mice. Mechanistically, T-AS1 directly bound to Myelin Protein Zero Like 1 (MPZL1). MPZL1 showed an oncogenic function in GC by promoting cell proliferation, migration and invasion but inhibiting cell apoptosis. High expression of MPZL1 was associated with poor survivor of GC patients. Knockdown of MPZL1 could abrogate the effect of T-AS1 in the tumor-promoting function. Conclusions: T-AS1 plays a pivotal oncogenic role in GC and is an independent prognostic factor for GC patients. The oncogenic function of T-AS1 is dependent on its direct downstream effector MPZL1.