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

Using a multidimensional genomic data set on glioblastoma from The Cancer Genome Atlas, we identified hsa-miR-26a as a cooperating component of a frequently occurring amplicon that also contains CDK4 and CENTG1, two oncogenes that regulate the RB1 and PI3 kinase/AKT pathways, respectively. By integrating DNA copy number, mRNA, microRNA, and DNA methylation data, we identified functionally relevant targets of miR-26a in glioblastoma, including PTEN, RB1, and MAP3K2/MEKK2. We demonstrate that miR-26a alone can transform cells and it promotes glioblastoma cell growth in vitro and in the mouse brain by decreasing PTEN, RB1, and MAP3K2/MEKK2 protein expression, thereby increasing AKT activation, promoting proliferation, and decreasing c-JUN N-terminal kinase-dependent apoptosis. Overexpression of miR-26a in PTEN-competent and PTEN-deficient glioblastoma cells promoted tumor growth in vivo, and it further increased growth in cells overexpressing CDK4 or CENTG1. Importantly, glioblastoma patients harboring this amplification displayed markedly decreased survival. Thus, hsa-miR-26a, CDK4, and CENTG1 comprise a functionally integrated oncomir/oncogene DNA cluster that promotes aggressiveness in human cancers by cooperatively targeting the RB1, PI3K/AKT, and JNK pathways.
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PMID:Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship. 2008 Jun 66

As the most fatal disease in human central nerve system, glioblastoma has attracted increasing attention. Unfortunately, the prognosis for patients with glioblastoma still quite unfavorable. Recent years, circular RNAs (circRNAs) have been identified to be associated with carcinogenesis due to their abnormal expression. However, the detailed molecular mechanism of circRNAs in regulating cancer progression is still unclear. This study focused on the potential mechanism of circ-PITX1 in glioblastoma. Herein, circ-PITX1 was found to be upregulated in glioblastoma and could mediate glioblastoma tissues and cell lines. Functionally, downregulation of circ-PITX1 hampered cell proliferation and accelerated cell apoptosis. Through mechanism investigation, we identified the cytoplasmic localization of circ-PITX1 and its molecular sponge role. The interactions between circ-PITX1 and miR-379-5p as well as between miR-379-5p and MAP3K2 were demonstrated. Thus, we confirmed that circ-PITX1 exerted as a competing endogenous RNA (ceRNA) in glioblastoma by sponging miR-379-5p to elevate MAP3K2 expression. Rescue assays demonstrated that MAP3K2 rescued the proliferation and apoptosis mediated by the silencing of circ-PITX1. Collectively, our study elucidated a novel molecular pathway and its functions in glioblastoma.
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PMID:Circular RNA circ-PITX1 promotes the progression of glioblastoma by acting as a competing endogenous RNA to regulate miR-379-5p/MAP3K2 axis. 3149 5