Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
Gene/Protein
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Query: UMLS:C0017636 (
glioblastoma
)
18,345
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The factors involved in cell differentiation have recently garnered interest for their role in inhibition of pathogenesis in various tumors. However, their role in
glioblastoma
(
GBM
) remains poorly understood. We analyzed The Cancer Genome Atlas (TCGA)
GBM
data and found significant downregulation of neurogenic differentiation factor
NeuroD2
in
GBM
patients. Low levels of
NeuroD2
were found to be correlated with poor overall survival of
GBM
patients in TCGA dataset as well as in our cohort. Interestingly,
NeuroD2
was shown to be transcriptionally induced by p53 and post-transcriptionally targeted by hypoxia- inducible miRNA, miR-210.
NeuroD2
overexpression diminished
GBM
aggressiveness by inhibiting cell proliferation, migration and promoting apoptosis under hypoxia.
NeuroD2
overexpressing
GBM
cells failed to form three-dimensional (3D)-tumor spheroids and displayed reduced migration in a 3D gelatin matrix.
NeuroD2
gene signature was enriched in pathways belonging to cytokine-cytokine receptor interaction, TNF-signaling, PI3K-AKT signaling, focal adhesion and ECM-receptor interaction. Overall, our study identifies a novel role of
NeuroD2
as a tumor suppressor and prognostic biomarker in
GBM
the levels of which are tightly regulated by p53 and miR-210. Overexpressing
NeuroD2
may potentially be a simple and efficient therapeutic strategy to inhibit the malignant phenotype of
GBM
cells.
...
PMID:p53 and miR-210 regulated NeuroD2, a neuronal basic helix-loop-helix transcription factor, is downregulated in glioblastoma patients and functions as a tumor suppressor under hypoxic microenvironment. 2922 33
The levels of microRNAs (miRNAs) are altered in various diseases including
glioblastoma
(
GBM
) and this alteration may have widespread effects on various hallmarks of cancer cells. MiR210 is overexpressed in
GBM
and functions as an oncogenic miRNA. Anti-miR210 therapy holds great promise but its efficient delivery remains a major challenge. Our work here explores a novel role of Tachyplesin (Tpl), a cell-penetrating antimicrobial peptide, as a nanocarrier for anti-miR210. Tpl electrostatically interacts with anti-miR210 at 1:25 and 1:50 (anti-miR:Tpl) weight ratios to form a complex and efficiently delivers anti-miR210 inside
GBM
cells cultured as 2D and 3D spheroid model. Treatment of
GBM
cells with the complex significantly inhibited miR210 levels (~90%), proliferation, migration and spheroid formation ability and induced apoptosis as evident by increased levels of caspase 3/7 and ROS.
GBM
cells pre-treated with anti-miR210:Tpl complex were also found to be sensitive to TMZ mediated action. Uptake of the complex in
GBM
cells induced the levels of miR210 targeted tumor suppressor genes,
NeuroD2
and HIF3A. Overall, our work reveals a novel and efficient miRNA delivery ability of Tpl in glioma cells, holding a great promise for treatment of
GBM
and potentially for other cancers.
...
PMID:Efficient delivery of anti-miR-210 using Tachyplesin, a cell penetrating peptide, for glioblastoma treatment. 3172 99
