Abstract
BackgroundRecently, 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.ResultsBy 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.ConclusionsTogether, 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.
Highlights
Increasing evidence shows that long noncoding RNAs play a significant role in human tumorigenesis
Our previous work found that CCAT1 could regulate cell proliferation and migration in esophageal squamous cell carcinoma and higher expression of CCAT1 is correlated with poorer outcomes [19]
We focused on overexpressed long noncoding RNAs (lncRNAs) because these lncRNAs may be more readily used as early diagnosis markers or therapeutic targets
Summary
Increasing evidence shows that long noncoding RNAs (lncRNAs) play a significant role in human tumorigenesis. The function of lncRNAs in human gastric cancer remains largely unknown. Gastric cancer research has mainly focused on the deregulation of protein-coding genes to identify oncogenes and tumor suppressors that could serve as diagnostic and therapeutic targets. LncRNAs are operationally defined as RNA transcripts that are > 200 nt with limited protein coding potential [6], which have been shown to play a key role in tumorigenesis, including GC [7,8,9]. Many studies found that lncRNAs could play an important role in regulating gene expression by different mechanisms, including chromatin modification, and transcriptional and posttranscriptional processing [10,11,12].
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