Antisense lncRNA NNT-AS1 Promoted Esophageal Squamous Cell Carcinoma Progression by Regulating Its Sense Gene NNT Expression

Abstract BackgroundAntisense lncRNAs were endogenous productions from the antisense strand of coding genes and transcribed in the opposite direction of sense gene. This study aimed to systematically evaluate the roles and functions of antisense lncRNAs in esophageal squamous cell carcinoma (ESCC).MethodsDifferentially expressed antisense lncRNAs were initially screened using transcriptome data from 119 paired ESCC samples in GSE53624, and were further validated in 6 paired ESCC samples from our institution. Log-rank test was adopted to identify ESCC prognosis associated lncRNAs. Finally, functional assays were performed to reveal the functions of our identified antisense lncRNAs. ResultsIn total, 174 antisense lncRNAs were differentially expressed in both GSE53624 and JSPH samples. Five of them were significantly associated with ESCC prognosis (NNT-AS1, NKILA, CCDC18-AS1, SLCO4A1-AS1 and AC110619.1). The upregulation of NNT-AS1 was validated in ESCC cell lines. Knockdown of NNT-AS1 inhibited ESCC cell proliferation, migration, and promoted ESCC cells apoptosis and induced cell cycle arrest in G2/M stage. NNT-AS1 expression was significantly correlated with its sense gene NNT and NNT-AS1 knockdown could suppress NNT expression. Inhibition of NNT suppressed ESCC cell proliferation and migration. Mechanically, NNT-AS1 served as a competing endogenous RNA to sponge the miR-382-5p, which could repress NNT expression. Pathway enrichment analysis and western blot assay indicated that NNT-AS1 and NNT could regulate the cell cycle pathway. ConclusionAntisense lncRNA NNT-AS1 promoted ECSS progression by targeting NNT through sponging miR-382-5p. This study provided us a deeper insight into the roles of antisense lncRNAs in ESCC and identified potential therapeutic targets.