Abstract
OBJECTIVES: To investigate the regulatory role and mechanism of long non-coding RNA LASTR in progression of head and neck squamous cell carcinoma (HNSCC). METHODS: LASTR expression in HNSCC and its correlation with patient prognosis were analyzed using TCGA and GEO transcriptomic data, and its expression in HNSCC cell lines was validated by qPCR. In a loss-of-function HNSCC cell model with siRNA-mediated LASTR knockdown, the changes in cell proliferation, migration, and invasion were assessed by high-content counting, CCK-8 assay, ATP detection, and Transwell assay. Bioinformatic analysis was conducted to identify the target genes of LASTR, and their interactions with BCAM were verified by qPCR and immunoblotting. The LASTR-miR-4476-BCAM regulatory axis was confirmed with RNA pulldown and dual-luciferase assays. The functional role of BCAM was investigated, and rescue experiments were performed to determine if BCAM mediates the effects of LASTR expression modulation. RESULTS: LASTR was significantly upregulated in HNSCC tissues and cell lines, and its high expression was significantly correlated with poor patient prognosis. In HNSCC cells, LASTR knockdown significantly suppressed cell proliferation, migration, and invasion. Bioinformatic analysis revealed 78 candidate target genes of LASTR, enriched in pathways involving angiogenesis, hypoxia response, MAPK, ErbB, and Ras signaling. LASTR knockdown obviously decreased BCAM expression HNSCC cells. Mechanistically, LASTR upregulated BCAM by sequestering miR-4476. BCAM knockdown similarly suppressed malignant phenotypes of HNSCC cells, and its overexpression rescued the inhibitory effects of LASTR knockdown. CONCLUSIONS: LASTR is upregulated in HNSCC and associated with poor prognosis. High expression of LASTR promotes HNSCC progression by acting as a ceRNA for miR-4476 to upregulate BCAM, suggesting the role of LASTR and BCAM as potential biomarkers and therapeutic targets for HNSCC.