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Erschienen in:
28.08.2019 | Original Article
DLX6-AS1/miR-204-5p/OCT1 positive feedback loop promotes tumor progression and epithelial–mesenchymal transition in gastric cancer
Erschienen in: Gastric Cancer | Ausgabe 2/2020
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Background
Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in progression of gastric cancer (GC). Nevertheless, the function and expression level of DLX6-AS1 in GC remain unknown.
Methods
We explored the sequencing data of DLX6-AS1 downloaded from The Cancer Genome Atlas. The expression of DLX6-AS1, miR-204-5p and OCT1 in 56 GC patients and GC cell lines was quantified by qRT-PCR and western blotting. Furthermore, we performed in vitro functional assays to assess proliferation, invasion and migration of GC cells by knockdown of DLX6-AS1. The expression level of epithelial–mesenchymal transition (EMT)-related genes was also determined by qRT-PCR and western blotting. Actin remodeling was detected by F-actin phalloidin staining. The luciferase reporter assay and chromatin immunoprecipitation assay was utilized to confirm the bioinformatic prediction. The function of the DLX6-AS1/miR-204-5p/OCT1 axis in GC proliferation was clarified by rescue assays.
Results
We first demonstrated that DLX6-AS1 was upregulated in GC tissues and cell lines and was associated with T3/T4 invasion, distant metastasis and poor clinical prognosis. Further functional analysis showed that downregulation of DLX6-AS1 inhibited GC cell proliferation, migration, invasion and EMT in vitro. Mechanistic investigation indicated that DLX6-AS1 acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-204-5p and upregulating OCT1. Moreover, the transcription factor OCT1 was confirmed to enhance DLX6-AS1 expression by targeting the promoter region.
Conclusions
This study revealed that OCT1-induced DLX6-AS1 promoted GC progression and the EMT via the miR-204-5p/OCT1 axis, suggesting that this lncRNA might be a promising prognostic biomarker and therapeutic target for GC.