Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MicroRNAs are approximately 21nt single-stranded RNAs and function as regulators of gene expression. Previous studies have shown that microRNAs play crucial roles in tumorigenesis by targeting the mRNAs of oncogenes or tumor suppressors. Here we show that brain-enriched miR-128 is down-regulated in glioma tissues and cell lines when compared to normal brain tissues. Overexpression of miR-128 in glioma cells inhibited cell proliferation. A bioinformatics search revealed a conserved target site within the 3'untranslated region (UTR) of E2F3a, a transcription factor that regulates cell cycle progression. The protein levels of E2F3a in gliomas and normal brain tissues were negatively correlated to the expression levels of miR-128 in these tissues. Overexpression of miR-128 suppressed a luciferase-reporter containing the E2F3a-3'UTR and reduced the level of E2F3a protein in T98G cells. Moreover, knocking down of E2F3a had similar effect as overexpression of miR-128, and overexpression of E2F3a can partly rescue the proliferation inhibition caused by miR-128. Taken together, our study demonstrates that miR-128 can inhibit proliferation of glioma cells through one of its targets, E2F3a.
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PMID:MicroRNA-128 inhibits glioma cells proliferation by targeting transcription factor E2F3a. 1881 Mar 76

Brain-enriched miR-128 is repressed in glioma cells, and could inhibit the proliferation of gliomas by targeting genes such as E2F3a and BMI1. To identify more targets of miR-128 in glioblastoma multiforme, the pulse stable isotope labeling with amino acids in cell culture (pSILAC) technique was used to test its impact on whole protein synthesis in T98G glioma cells. We successfully identified 1897 proteins, of which 1459 proteins were quantified. Among them, 133 proteins were downregulated after the overexpression of miR-128. Through predictions using various bioinformatics tools, 13 candidate target genes were chosen. A luciferase assay validated that 11 of 13 selected genes were potential targets of miR-128, and a mutagenesis experiment confirmed CBFB, CORO1C, GLTP, HnRNPF, and TROVE2 as the target genes. Moreover, we observed that the expression of CORO1C, TROVE2, and HnRNPF were higher in glioma cell lines compared to normal brain tissues and presented a tendency toward downregulation after overexpression of miR-128 in T98G cells. Furthermore, we have validated that CORO1C, TROVE2, and HnRNPF could inhibit glioma cell proliferation. In sum, our data showed that the integration of pSILAC and bioinformatics analysis was an efficient method for seeking the targets of miRNAs, and plentiful targets of miR-128 were screened and laid the foundation for research into the miR-128 regulation network.
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PMID:Proteomic screening and identification of microRNA-128 targets in glioma cells. 2578 Dec 72

E2F3a, as a member of the E2F family, is essential for cell division associated with the progression of many cancers. However, the biological effect of E2F3a on glioma is not understood as well. To investigate the functional mechanism of E2F3a in glioma, we examined the expression of E2F3a in glioma tissue and cell lines. We found that E2F3a was upregulated in glioma tissue compared with adjacent tissue, and this was associated with a poor survival rate. E2F3a was highly expressed in glioma cell lines compared with normal HEB cell lines. Knockdown of E2F3a significantly inhibited cell proliferation, promoted G0/G1 phase arrest, elevated apoptosis rates, and suppressed cell migration and invasion. However, overexpression of E2F3a markedly promoted cell proliferation, migration, and invasion and inhibited apoptosis. Moreover, in vivo studies showed that knockdown of E2F3a expression dramatically inhibited U373 tumor growth in a nude mouse model. Results of real-time PCR and Western blot showed that the depletion of E2F3a upregulated the expression levels of cell apoptosis-related proteins and downregulated migration-related proteins. Conversely, E2F3a overexpression downregulated the expression levels of cell apoptosis-related proteins and upregulated migration-related proteins. In conclusion, our results highlight the importance of E2F3a in glioma and provide new insights into the diagnostics and therapeutics of gliomas.
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PMID:Knockdown of E2F3 Inhibits Proliferation, Migration, and Invasion and Increases Apoptosis in Glioma Cells. 2833 65