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

Abstract

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.