Conclusion
This is the first report of LncRNA GAS5 acting as a tumor suppressor in LSCC by regulating the miR-26a-5p/ULK2 axis, and it could be a new target for gene therapy in LSCC.
Methods
Cell viability and apoptosis were, respectively, detected by cell counting kit-8 and flow cytometry, DIANA-LncBase V, Starbase, TargetScan and a dual-luciferase reporter gene assay were employed to assess the relationship among GAS5, miR-26a-5p and uncoordinated 51-like kinase 1 (ULK2), and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot were performed to detect the expression of autophagy-relative factors.
Purpose
Long noncoding RNAs growth arrest-specific 5 (GAS5) exerts important functions in modulating various tumor behaviors. However, the role of lncRNA GAS5 in laryngeal squamous cell carcinoma (LSCC) remains unknown. Materials and
Results
The expression level of GAS5 was frequently decreased in LSCC cell lines, and up-regulated GAS5 inhibited AMC-HN-8 cells viability and induced apoptosis. More importantly, we found that GAS5 activated autophagy, with enhanced autophagy-related proteins after GAS5 overexpression. While down-regulated GAS5 had opposite results in Tu 177 cells, GAS5 was found to act as a microRNA sponge in a pathway to regulate miR-26a-5p and its target gene ULK2. MiR-26a-5p mimics inhibited apoptosis and autophagy, which were reversed by GAS5 and siGAS5 in AMC-HN-8 cells and Tu 177 cells, as well as ULK2 in AMC-HN-8 cells. Meanwhile, the concomitant downregulation of ULK2 and miRNA-26a-5p inhibitor decreased the miRNA-26a-5p inhibitor-induced apoptosis and autophagy.