Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis

Abstract

Abstract The goal of this study was to demonstrate the functions and specific mechanism of long non-coding RNA (lncRNA) GNAS-AS1 in lung adenocarcinoma. Levels of lncRNA GNAS-AS1, microRNA (miR)-433-3p, and Rab3A were assessed by quantitative real-time PCR (qRT-PCR). The target-binding sites of lncRNA GNAS-AS1, miR-433-3p, and Rab3A were predicted and confirmed by bioinformatics tool (StarBase) and a dual-luciferase reporter system. Cell proliferation and apoptosis were checked using MTT and flow cytometry, respectively. Additionally, the levels of apoptosis-related and epithelial–mesenchymal transition (EMT)-associated genes in A549 cells were analyzed by qRT-PCR and western blot. We found that lncRNA GNAS-AS1 was upregulated, miR-433-3p was low-expressed, and Rab3A was overexpressed in lung adenocarcinoma tissues and cell lines. LncRNA GNAS-AS1 interacted with miR-433-3p and negatively regulated miR-433-3p levels. Rab3A was a direct target of miR-433-3p. Downregulation of lncRNA GNAS-AS1 remarkably suppressed cell proliferation, promoted cell apoptosis, decreased B-cell lymphoma-2 (Bcl-2) expression, enhanced the Bcl-2-Associated X (Bax) level, promoted E-cadherin expression, and reduced N-cadherin and Rab3A levels. However, the miR-433-3p inhibitor reversed all these findings. Similarly, the inhibitory effects of miR-433-3p mimic on A549 cells were reversed by the Rab3A-plasmid. In conclusion, lncRNA GNAS-AS1 downregulation suppressed lung adenocarcinoma cell proliferation and EMT through the miR-433-3p/Rab3A axis.