LINC02774 inhibits glycolysis in glioma to destabilize HIF-1α dependent on transcription factor RP58.

Glioma, the most common of malignant tumors in the brain, is responsible for the majority of deaths from primary brain tumors. The regulation of long noncoding RNAs (lncRNAs) in HIF-1α-driven tumor development remains unclear. LINC02774 is a nuclear lncRNA and that it is being reported for the first time in this study. We found the downregulation of LINC02774 in glioma and decreased with the degree of malignant, with its expression showing a negative correlation with the relative index of enhanced magnetic resonance (RIEMR). RIEMR-associated LINC02774 was found to inhibit glycolysis by modulating the hypoxia pathway rather than the hypoxia response itself. LINC02774 interacted with its neighboring gene, RP58 (ZBTB18), to enhance the expression of PHD3, which catalyzed HIF-1α hydroxylase and ubiquitination, leading to the downregulation of HIF-1α expression. We also found that the function of LINC02774, dependent on PHD3, was diminished upon RP58 depletion. Notably, higher expression of RIEMR-associated LINC02774 was associated with a favorable prognosis. In conclusion, these findings reveal the role of RIEMR-associated LINC02774, which relies on its neighbor gene, RP58, to regulate the hypoxia pathway as a novel tumor suppressor, suggesting its potential to be a prognostic marker and a molecular target for the therapy of glioma.