Long non-coding RNA GAS6-AS1 acts as a ceRNA for microRNA-585, thereby increasing EIF5A2 expression and facilitating hepatocellular carcinoma oncogenicity

Abstract

ABSTRACT Long non-coding RNA termed GAS6 antisense RNA 1 (GAS6-AS1) plays an essential role in gastric and non-small cell lung cancers. Nonetheless, the function of GAS6-AS1 in hepatocellular carcinoma (HCC) has not been so far studied in detail. In this study, reverse-transcription quantitative PCR was performed to measure GAS6-AS1 expression in HCC samples. A series of functional experiments, including MTT assay, colony formation assay, flow-cytometric analysis, and transwell migration and invasion assays, was performed to determine the influence of GAS6-AS1 knockdown on the malignant phenotype of HCC. The results showed that GAS6-AS1 was significantly upregulated in HCC tissue samples and cell lines. Increased GAS6-AS1 expression was associated with tumor size, Edmondson grade, and Tumor-Node-Metastasis (TNM) stage among patients with HCC. The overall survival of patients with HCC characterized with high expression of GAS6-AS1 was significantly shorter in comparison to that of patients with low level of GAS6-AS1. Functional experiments indicated that knockdown of GAS6-AS1 suppressed HCC cell proliferation, colony formation, migration, and invasion in vitro; promoted apoptosis in vitro; and decreased tumor growth in vivo. Of note, GAS6-AS1 was validated as a competing endogenous RNA (ceRNA) for microRNA-585 (miR-585) and consequently increased the expression of eukaryotic translation initiation factor 5A2 (EIF5A2). Finally, rescue experiments confirmed the association among GAS6-AS1, miR-585, and EIF5A2 in HCC cells. Our study provides substantial evidence that the GAS6-AS1/miR-585/EIF5A2 pathway plays an important role in HCC progression and that might be considered as a potential target for therapeutic approaches in HCC.