MicroRNAs (miRNAs) are small, non‑coding RNAs which regulate gene expression at the post-transcriptional level. Abnormal expression of miRNAs occurs frequently in tumors. Although the two miRNAs miR‑24‑3p and miR‑27a‑3p come from two duplicated gene clusters of miR‑23a~27a~24‑2 and miR‑23b~27b~24‑1 which are found to be deregulated in a variety of cancers, the role of cooperation of the two clusters and the function of the two miRNAs in tumors have not been completely characterized. Here, we show that overexpression of miR‑24‑3p and miR‑27a‑3p could promote cell proliferation using the MTT assay. By integrated bioinformatic analysis and experimental confirmation, we identified MXI1, which has been found to act as a tumor suppressor gene by affecting c‑Myc, as a direct target of miR‑24‑3p and miR‑27a‑3p. While targeting the MXI1 3' untranslated region by miR‑24‑3p or miR‑27a‑3p, luciferase activity was attenuated. The two miRNAs promote glioma cell proliferation via targeting MXI1 and the experiment was confirmed by the rescue experiments. Furthermore, our results show that two clusters of miR-23a~27a~24-2 and miR‑23b~27b~24‑1 regulate MXI1 synergistically. These findings reveal, for the first time, the novel functions of cooperation of miR‑24‑3p and miR‑27a‑3p from two clusters in promoting cell proliferation through MXI1. Additionally, we observed that miR‑27a‑3p is upregulated in glioma tissues.
Glioma is the most common malignant tumor in the central nervous system. This study aims to explore the potential mechanism and identify gene signatures of glioma. The glioma gene expression profile GSE4290 was analyzed for differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied for the enriched pathways. A protein-protein interaction (PPI) network was constructed to find the hub genes. Survival analysis was conducted to screen and validate critical genes. In this study, 775 downregulated DEGs were identified. GO analysis demonstrated that the DEGs were enriched in cellular protein modification, regulation of cell communication, and regulation of signaling. KEGG analysis indicated that the DEGs were enriched in the MAPK signaling pathway, endocytosis, oxytocin signaling, and calcium signaling. PPI network and module analysis found 12 hub genes, which were enriched in synaptic vesicle cycling rheumatoid arthritis and collecting duct acid secretion. The four key genes CDK17, GNA13, PHF21A, and MTHFD2 were identified in both generation (GSE4412) and validation (GSE4271) dataset, respectively. Regression analysis showed that CDK13, PHF21A, and MTHFD2 were independent predictors. The results suggested that CDK17, GNA13, PHF21A, and MTHFD2 might play important roles and potentially be valuable in the prognosis and treatment of glioma.
Departmental sources Background:The extent of glioma resection influences the overall survival (OS) and progression-free survival (PFS). Ferroptosis is a newly recognized type of cell death, which may be associated with low-grade glioma border detection and OS. This study is assessed an optimized ferroptosis gene panel for glioma treatment. Material/Methods:We obtained 45 reports on ferroptosis-related proteins in PubMed and conducted a statistical test of the patients' overall survival (OS) in the TCGA GBMLGG and CGGA databases. The statistically significant genes were screened for an optimal panel, followed by GO and KEGG analysis and evaluated its correlation with known prognostic factors of glioma, including IDH1 mutation, methylated MGMT, tumor purity, 1p/19q LOH, and methionine cycle. Results:Eight genes panel (ALOX5, CISD1, FTL, CD44, FANCD2, NFE2L2, SLC1A5, and GOT1) were highly related to OS (P<0.001) and PFS (P<0.001) of low-grade glioma (LGG) patients, out of which 6 genes (ALOX5, CISD1, CD44, FTL, FANCD2, and SLC1A5) were correlated with IDH1_p.R132H (P<0.001) and 5 genes (ALOX5, CD44, FTL, NFE2L2, SLC1A5) showed a correlation with tumor purity (P<0.001). Five genes (ALOX5, CD44, CISD1, FTL, and SLC1A5) were associated with methylated MGMT (P<0.001), out of which 6 genes (ALOX5, CD44, FANCD2, NFE2L2, SLC1A5, and GOT1) had significantly different expression in healthy brain tissue vs. glioma (P<0.001). Conclusions:Our panel of 8 ferroptosis genes showed a significant correlation with the diagnostic and prognostic factors of low-grade glioma and can be applied in neuroradiology and surgery.
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