LncRNA NUTM2A-AS1 positively modulates TET1 and HIF-1A to enhance gastric cancer tumorigenesis and drug resistance by sponging miR-376a.

Long noncoding RNA NUTM2A-AS1 has been shown to be dysregulated in non-small cell lung carcinoma. To date, it is unclear whether NUTM2A-AS1 plays a role in gastric cancer progression. The purpose of this study is to elucidate the molecular mechanism of the role of NUTM2A-AS1 in gastric cancer. mRNA and protein levels were measured by RT-qPCR and western blot methods. Invasion ability was examined by transwell assay. Cell viability was determined by MTT assay. Dual-luciferase assay, RNA pull down, and RNA immunoprecipitation were used to confirm direct binding of between miR-376a and NUTM2A-AS1 or TET1. Xenografting tumor assay and TCGA analysis showed the contributory role of NUTM2A-AS1 in vivo and human clinical setting. Our results suggested that NUTM2A-AS1 promoted cell viability, invasion, and drug resistance of gastric cancer cells, which was largely rescued by miR-376a. More interestingly, TET1 and HIF-1A were negatively regulated by miR-376a. TET1 could interact with HIF-1A to modulate PD-L1. Finally, we revealed that PD-L1 was key to NUTM2A-AS1- and miR-376a-mediated tumorigenesis and drug resistance. In summary, our conclusions facilitate us understand the underlying mechanism and develop novel treatment strategy for gastric cancer.