Long Non-Coding RNA PVT1 Enhances Glycolysis in Thyroid Carcinoma by Stabilizing HIF-1α and Activating Glycolytic Gene Transcription.

As the foremost endocrine system cancer, thyroid carcinoma exhibits an accelerating epidemiological trend across populations. Despite advances in treatment modalities, recurrence and metastasis remain challenges. The long non-coding RNA PVT1 (lncPVT1) has emerged as a conserved oncogenic regulator in multiple cancer types, yet its specific function in TC requires further exploration. Our research focused on examining how lncPVT1 affects glycolysis under both normoxic and hypoxic conditions using TC cell lines TPC-1 and K1. Overexpression of lncPVT1 significantly enhanced glucose consumption and lactate production under hypoxia, corroborating its ability to augment glycolysis. Further, lncPVT1 upregulated key glycolytic genes such as GLUT1, HK1, HK2, and PGK1, and facilitated TC cell proliferation. Mechanistically, lncPVT1 stabilized hypoxia-inducible factor 1α (HIF-1α) by impeding its degradation and leading to its accumulation. This accumulated HIF-1α then bound to specific regulatory sequences that control the expression of genes involved in glycolysis, ultimately activating these genes and boosting glycolytic activity. Our findings demonstrate that lncPVT1 regulates HIF-1α stability and glycolytic gene expression, advancing our understanding of TC metabolism and potentially revealing novel therapeutic targets.