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Three human glioma stem cell lines sorted for CD133 and one human neural precursor line sorted for CD133 to identify tumor-specific miRNA dysregulation

ABSTRACT: Several novel potential oncogenic and tumor suppressor miRNAs were identified by using the appropriate controls for stem cells. Expression profiles for human miRNAs in six samples were generated. The Agilent platform GPL7731 was used to analyze six RNA samples: CD133- human NPC, CD133+ human NPC, CD133- B4 glioma, CD133+ B4 Glioma, CD133+ NCH441 glioma, CD133+ NCH644 glioma

ORGANISM(S): Homo sapiens

SUBMITTER: Abounader Roger

PROVIDER: S-ECPF-GEOD-49470 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:Adverse effect of alcohol on neural function has been well documented. Especially, the teratogenic effect of alcohol on neurodevelopment during embryogenesis has been demonstrated in various models, which could be a pathologic basis for fetal alcohol spectrum disorders (FASDs). While the developmental defects from alcohol abuse during gestation have been described, the specific mechanisms by which alcohol mediates these injuries have yet to be determined. Recent studies have shown that alcohol has significant effect on molecular and cellular regulatory mechanisms in embryonic stem cell (ESC) differentiation including genes involved in neural development. To test our hypothesis that alcohol induces molecular alterations during neural differentiation we have derived neural precursor cells from pluripotent human ESCs in the presence or absence of ethanol treatment. Genome-wide transcriptomic profiling identified molecular alterations induced by ethanol exposure during neural differentiation of hESCs into neural rosettes and neural precursor cell populations. The Database for Annotation, Visualization and Integrated Discovery (DAVID) functional analysis on significantly altered genes showed potential ethanol's effect on JAK-STAT signaling pathway, neuroactive ligand-receptor interaction, Toll-like receptor (TLR) signaling pathway, cytokine-cytokine receptor interaction and regulation of autophagy. We have further quantitatively verified ethanol-induced alterations of selected candidate genes. Among verified genes we further examined the expression of P2RX3, which is associated with nociception, a peripheral pain response. We found ethanol significantly reduced the level of P2RX3 in undifferentiated hESCs, but induced the level of P2RX3 mRNA and protein in hESC-derived NPCs. Our result suggests ethanol-induced dysregulation of P2RX3 along with alterations in molecules involved in neural activity such as neuroactive ligand-receptor interaction may be a molecular event associated with alcohol-related peripheral neuropathy of an enhanced nociceptive response.

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Three human glioma stem cell lines sorted for CD133 and one human neural precursor line sorted for CD133 to identify tumor-specific miRNA dysregulation

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