A novel long noncoding RNA HOXC-AS3 mediates tumorigenesis of gastric cancer by binding to YBX1

Abstract

Background: Recently, increasing evidence shows that long noncoding RNAs (lncRNAs) play a significant role in human tumorigenesis. However, the function of lncRNAs in human gastric cancer remains largely unknown. Results: By using publicly available expression profiling data from gastric cancer and integrating bioinformatics analyses, we screen and identify a novel lncRNA, HOXC-AS3. HOXC-AS3 is significantly increased in gastric cancer tissues and is correlated with clinical outcomes of gastric cancer. In addition, HOXC-AS3 regulates cell proliferation and migration both in vitro and in vivo. RNA-seq analysis reveals that HOXC-AS3 knockdown preferentially affects genes that are linked to proliferation and migration. Mechanistically, we find that HOXC-AS3 is obviously activated by gain of H3K4me3 and H3K27ac, both in cells and in tissues. RNA pull-down mass spectrometry analysis identifies that YBX1 interacts with HOXC-AS3, and RNA-seq analysis finds a marked overlap in genes differentially expressed after YBX1 knockdown and those transcriptionally regulated by HOXC-AS3, suggesting that YBX1 participates in HOXC-AS3-mediated gene transcriptional regulation in the tumorigenesis of gastric cancer. Conclusions: Together, our data demonstrate that abnormal histone modification-activated HOXC-AS3 may play important roles in gastric cancer oncogenesis and may serve as a target for gastric cancer diagnosis and therapy.