Abstract
Gastric cancer (GC) is one of the most prevalent gastrointestinal malignancies. Long noncoding RNA (lncRNA) DANCR is a newly identified oncogenic lncRNA. However, the functional role and underlying molecular mechanisms of DANCR involved in GC progress remain unclear. In the present study, we investigated the biological function and underlying mechanisms of DANCR in GC cell migration and invasion. The results showed that knockdown of DANCR inhibited migration and invasion of GC cells, whereas overexpression of DANCR showed the opposite effect. Further investigation demonstrated that lncRNA-LET was a bona fide target gene of DANCR. In addition, high DANCR and low lncRNA-LET were significantly correlated with lymph node metastasis and late clinical stage. DANCR associated with EZH2 and HDAC3 to epigenetically silence lncRNA-LET and then regulated GC migration and invasion. Taken together, these findings indicate an important role for DANCR–lncRNA-LET axis in GC cell migration and invasion, and reveal a novel epigenetic mechanism for lncRNA-LET silencing.
Highlights
Gastric cancer (GC) is one of the most prevalent gastrointestinal malignancies and ranks the second leading cause of cancer-related deaths around the world [1]
The quantitative real-time PCR (qPCR) results showed that both siDANCR-1 and siDANCR-2 significantly decreased the DANCR expression in BGC-823 cells, whereas DANCR is markedly up-regulated in Gastric Adenocarcinoma cell line (AGS) cells with DANCR overexpression compared with those transfected with empty vector (Figure 1B)
The results showed that using siRNA against EZH2 or histone deacetylase 3 (HDAC3) alone partially rescued the long noncoding RNA (lncRNA)-LET suppression induced by DANCR overexpression, and combination of EZH2 and HDA3 siRNAs almost abolished the DANCR-mediated suppression of lncRNA-LET
Summary
Gastric cancer (GC) is one of the most prevalent gastrointestinal malignancies and ranks the second leading cause of cancer-related deaths around the world [1]. Several studies have demonstrated that TGF-β, ERK1/2, and NF-κB signaling pathways are implicated in the regulation of GC metastasis [3,4,5]. LncRNAs play important roles in regulating cell proliferation, differentiation, migration, invasion, and autophagy [8,9,10]. Up-regulation of oncogenic lncRNA MALAT1 is closely associated with densities of vasculogenic mimicry and endothelial vessels, and MALAT1 facilitates GC cell migration, invasion, metastasis, and vasculogenic mimicry through regulation of VE-cadherin, β-catenin, MMP-2, and MMP-9 [11]. LncRNA UCA1 is specially increased in GC tissues and related with poor prognosis of GC patients. UCA1 enhances GC growth and metastasis, and is involved in TGF-β-induced epithelial–mesenchymal transition (EMT) [12].
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