LncRNA GSEC impedes the reprogramming of glucose metabolism in papillary thyroid carcinoma by inhibiting the IGF2BP2/GLUT1 axis.

OBJECTIVE: To investigate the expression pattern of lncRNA GSEC in papillary thyroid carcinoma (PTC) and elucidate its functional role and molecular mechanism in regulating glycolytic metabolism and malignant progression.

MATERIALS AND METHODS: The expression levels of the GSEC gene in thyroid cancer were determined through bioinformatics analysis of the TCGA database, and potential downstream regulatory genes were predicted. GSEC mRNA levels in normal thyroid cells and thyroid cancer cells were detected by qRT-PCR. Cellular functions, including proliferation, invasion, and migration, were evaluated using CCK-8 assays, Annexin-V/PI staining, western blot, EdU staining, Transwell assays, and scratch tests. Glycolytic activity was assessed by western blot, glucose uptake assays, and measurements of extracellular lactate levels. Subcutaneous and metastatic papillary thyroid carcinoma (PTC) models were established in nude mice to investigate the effects of lncRNA GSEC expression on tumor growth and metastasis.

RESULTS: LncRNA GSEC expression was significantly downregulated in thyroid cancer. Overexpression of GSEC in PTC-1 cells effectively inhibited their proliferation, invasion, and migration. GSEC downregulated GLUT1 expression by inhibiting IGF2BP2, thereby disrupting glycolysis and suppressing tumor growth and invasion. In vivo assay demonstrated that GSEC overexpression significantly reduced tumor glycolysis, retarded tumor growth, and inhibited metastasis.

CONCLUSION: LncRNA GSEC is a key factor in the progression of PTC. By modulating the IGF2BP2/GLUT1 axis, GSEC affects cancer cell glycolysis, presenting a new potential target for metabolic intervention strategies.