Elevated Hexose-6-Phosphate Dehydrogenase Regulated by OSMR-AS1/hsa-miR-516b-5p Axis Correlates with Poor Prognosis and Dendritic Cells Infiltration of Glioblastoma

• Published in: Brain sciences Vol. 12; no. 8; p. 1012
• Main Authors: Zhang, Yi-Bin, Zheng, Shu-Fa, Ma, Lin-Jie, Lin, Peng, Shang-Guan, Huang-Cheng, Lin, Yuan-Xiang, Kang, De-Zhi, Yao, Pei-Sen
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 30.07.2022; MDPI
• Subjects: Brain cancer; Brain tumors; Breast cancer; ceRNA network; Dehydrogenases; Dendritic cells; Gene expression; Genomes; Genotypes; Glioblastoma; Glioma; H6PD; Hexose; Hypotheses; Immune checkpoint; immune infiltration; Infiltration; Medical prognosis; Metastases; MicroRNAs; outcome; Prognosis; Survival analysis; Austria
• ISSN: 2076-3425; 2076-3425
• DOI: 10.3390/brainsci12081012

Objective Glioblastoma (GBM), a type of malignant glioma, is the most aggressive type of brain tumor and is associated with high mortality. Hexose-6-phosphate dehydrogenase (H6PD) has been detected in multiple tumors and is involved in tumor initiation and progression. However, the specific role and mechanism of H6PD in GBM remain unclear. Methods We performed pan-cancer analysis of expression and prognosis of H6PD in GBM using the Genotype-Tissue Expression Project (GTEx) and The Cancer Genome Atlas (TCGA). Subsequently, noncoding RNAs regulating H6PD expression were obtained by comprehensive analysis, including gene expression, prognosis, correlation, and immune infiltration. Finally, tumor immune infiltrates related to H6PD and survival were performed. Results Higher expression of H6PD was statistically significantly associated with an unfavorable outcome in GBM. Downregulation of hsa-miR-124-3p and hsa-miR-516b-5p in GBM was detected from GSE90603. Subsequently, OSMR-AS1 was observed in the regulation of H6PD via hsa-miR-516b-5p. Moreover, higher H6PD expression significantly correlated with immune infiltration of dendritic cells, immune checkpoint expression, and biomarkers of dendritic cells. Conclusions The OSMR-AS1/ miR-516b-5p axis was identified as the highest-potential upstream ncRNA-related pathway of H6PD in GBM. Furthermore, the present findings demonstrated that H6PD blockading might possess antitumor roles via regulating dendritic cell infiltration and immune checkpoint expression.