Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Noncoding RNAs regulate transcription of gene expression and play an important role in the pathogenesis of glioblastomas. These tumors are heterogeneous with some glioma stem cells (GSCs) that are highly tumorigenic subpopulations of cells contributing to recurrence and treatment resistance. In this study, GSCs were established by neurosphere cultures of primary glioblastoma cells and validated by the expression of GSC marker CD133. The expression of the long noncoding RNA HOTAIRM1 was detected using real-time quantitative reverse transcription PCR (qRT-PCR). The role of HOTAIRM1 in the proliferation, apoptosis, stemness, and tumorigenicity of GSCs was investigated by soft agar colony formation, flow cytometry, TUNEL analysis, sphere formation, and in vivo xenograft models through silencing of HOTAIRM1. The expression of HOTAIRM1 and the neighboring HOX genes were analyzed by qRT-PCR in different grades of gliomas and nontumor tissues. We found that HOTAIRM1 is significantly elevated in GSCs. The silencing of HOTAIRM1 significantly impairs the proliferation, apoptosis, self-renewal, tumorigenesis of GSCs. In addition, HOTAIRM1 is significantly upregulated in gliomas and associated with tumor grade and patient survival. HOTAIRM1 neighboring genes, HOXA1, HOXA2, and HOXA3, are also significantly upregulated in gliomas and correlate with the expression of HOTAIRM1. Among them, HOXA2 and HOXA3 were identified as being upregulated in GSCs and contributed to the self-renewal of these stem cells. Taken together, our results demonstrate that HOTAIRM1 plays a critical role in the self-renewal of GSCs. These data also suggest that overexpression of HOTAIRM1 can be a negative prognostic factor for patient survival in malignant glioma and may be a promising potential therapeutic target.
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PMID:Long Noncoding RNA HOTAIRM1 Maintains Tumorigenicity of Glioblastoma Stem-Like Cells Through Regulation of HOX Gene Expression. 3169 Nov 27

Glioblastoma (GBM) is the most frequent malignant brain tumor in adults. Our study focused on uncovering differentially expressed genes (DEGs) and their methylation in order to identify novel diagnostic biomarkers and potential treatment targets. Using GBM RNA-sequencing data from The Cancer Genome Atlas (TCGA) database, DEGs between GBM samples and paracancer tissue samples were analyzed. Enrichment analysis for DEGs and transcription factors (TFs) was performed. A total of 1029 upregulated genes and 1542 downregulated genes were identified, which were associated mainly with multiple tumor-related and immune-related pathways such as cell cycle, mitogen-activated protein kinase signaling pathway, leukocyte transendothelial migration, and autoimmune thyroid disease. These DEGs were enriched for 174 TFs, and six TFs were differentially expressed and identified as key TFs in GBM: HOXA3, EN1, ZIC1, and FOXD3 were upregulated, while HLF and EGR3 were downregulated. A total of 1978 DEGs were involved in the regulatory networks of the six key differentially expressed TFs. High expression of EN1 was associated with shorter overall survival, while high expression of EGR3 was associated with shorter recurrence-free survival. The six TFs were differentially methylated in GBM samples compared with paracancer tissues. Our study identifies numerous DEGs and their associated pathways as potential contributors to GBM, particularly the TFs EN1, EGR3, HOXA3, ZIC1, FOXD3, and HLF. The differential expression of these TFs may be unlikely driven by aberrant methylation. These TFs may be useful as diagnostic markers and treatment targets in GBM, and EN1 and EGR3 may have predictive prognostic value.
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PMID:Identification of Key Differentially Expressed Transcription Factors in Glioblastoma. 3261 55