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LINC02774 inhibits glycolysis in glioma to destabilize HIF-1α dependent on transcription factor RP58
Yuanbing Chen1,2,3, Yating Liu4,5, Jianbing Xiong6
1Department of Neurosurgery Third Xiangya Hospital, Central South University Changsha Hunan China.
Abstract:
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.
Insights
This study identifies LINC02774 as a novel tumor suppressor in glioma. Its downregulation correlates with malignancy, and it inhibits tumor growth by regulating the hypoxia pathway via RP58 and PHD3.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioma is the most common malignant brain tumor, with unclear regulation mechanisms in tumor development.
- Long noncoding RNAs (lncRNAs) role in hypoxia-inducible factor 1-alpha (HIF-1α)-driven glioma remains largely unknown.
- LINC02774 is a newly identified nuclear lncRNA with potential involvement in glioma pathogenesis.
Purpose of the Study:
- To investigate the role and mechanism of LINC02774 in glioma development.
- To explore the relationship between LINC02774 expression, tumor malignancy, and clinical outcomes.
- To elucidate the molecular pathway regulated by LINC02774 in glioma.
Main Methods:
- Analysis of LINC02774 expression in glioma tissues and correlation with clinicopathological features.
- Investigation of LINC02774's interaction with RP58 and its effect on PHD3 and HIF-1α.
- Assessment of LINC02774's impact on glycolysis and tumor progression.
- Correlation of LINC02774 expression with relative index of enhanced magnetic resonance (RIEMR) and patient prognosis.
Main Results:
- LINC02774 was downregulated in glioma, with expression decreasing as malignancy increased.
- LINC02774 expression negatively correlated with RIEMR and inhibited glycolysis by modulating the hypoxia pathway.
- LINC02774 interacted with RP58 to upregulate PHD3, leading to HIF-1α downregulation.
- Higher LINC02774 expression was associated with a favorable prognosis in glioma patients.
Conclusions:
- LINC02774 acts as a tumor suppressor in glioma by regulating the hypoxia pathway through RP58 and PHD3.
- LINC02774's function is dependent on RP58 and PHD3, highlighting a novel regulatory mechanism.
- LINC02774 shows potential as a prognostic biomarker and therapeutic target for glioma.
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