c-Myc-dependent LAMP3 regulates the proliferation, metastasis and metabolic reprogramming of tongue squamous cell carcinoma.

To delve into the role and molecular mechanism of lysosome-associated membrane protein 3 (LAMP3) in tongue squamous cell carcinoma (TSCC). Differential expression of LAMP3 in TSCC from GEO microarray was analyzed, and pathway enrichment analysis of LAMP3 was performed utilizing GSEA. LAMP3 expression was detected by western blot, immumohistochemical staining and qRT-PCR. LAMP3 knockdown plasmid was constructed for a variety of biological function assays to verify the involvement of LAMP3 in TSCC. The upstream transcription factors and binding sites of LAMP3 were bioinformatically predicted. Dual luciferase reporter gene assay was applied to check the presence of c-Myc binding to the promoter region of LAMP3 and the regulation of its transcription. Further, a xenograft tumor model was developed to corroborate the impact of LAMP3 on tumor growth in vivo. LAMP3 expression was enhanced in TSCC tissues and cells. LAMP3 knockdown attenuated TSCC cell proliferation, DNA replication and metastatic capacity while induced glucose metabolism reprogramming in vitro. Meanwhile, LAMP3 depletion contributed to the delay of tumor progression in vivo. c-Myc was found bind to the LAMP3 promoter region to positively modulate LAMP3 transcriptional expression. LAMP3 regulated by c-Myc enhanced TSCC cell proliferation, DNA replication capacity while induced glucose metabolism reprogramming, suggesting a potential target for clinical trials in TSCC.