Over-expressed long noncoding RNA HOXA11-AS promotes cell cycle progression and metastasis in gastric cancer.

ABSTRACT

BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as critical regulators in a variety of human cancers, including gastric cancer (GC). However, the function and mechanisms responsible for these molecules in GC are not fully understood. In our previous study, we found that GC associated lncRNA HOXA11-AS is significantly upregulated in GC tissues. Over-expressed HOXA11-AS promotes GC cells proliferation and invasion through scaffolding the chromatin modification factors PRC2, LSD1 and DNMT1. METHODS: HOXA11-AS expression levels in GC cells was detected by quantitative real-time PCR (qPCR). HOXA11-AS siRNAs and overexpression vector were transfected into GC cells to down-regulate or up-regulate HOXA11-AS expression. In vitro and in vivo assays were performed to investigate the functional role of HOXA11-AS in GC cells cell cycle progression, invasion and metastasis. RIP and ChIP assays were used to determine the mechanism of HOXA11-AS's regulation of underlying targets. RESULTS: We found that knockdown of HOXA11-AS induced GC cells G0/G1 phase arrest and suppressed GC cells migration, invasion and metastasis in vivo. Moreover, mechanistic investigation showed that HOXA11-AS could interact with WDR5 and promote ß-catenin transcription, bind with EZH2 and repress P21 transcription, and induce KLF2 mRNA degradation via interacting with STAU1. CONCLUSIONS: Taken together, these findings show that HOXA11-AS not only could promote GC cells migration and invasion in vitro, but also promotes GC cells metastasis in vivo, at least in part, by regulating ß-catenin and KLF2.