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| Status |
Public on Apr 10, 2020 |
| Title |
MiR-1253 exerts tumor-suppressive effects in medulloblastoma via inhibition of CDK6 and CD276 (B7-H3) (Infinium MethylationEPIC dataset) |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Of the four primary subgroups of medulloblastoma, the most frequent cytogenetic abnormality, i17q, distinguishes Groups 3 and 4 which carry the highest mortality; haploinsufficiency of 17p13.3 is a marker for particularly poor prognosis. At the terminal end of this locus lies miR-1253, a brain-enriched microR that regulates bone morphogenic proteins during cerebellar development. We hypothesized miR-1253 confers novel tumor-suppressive properties in medulloblastoma. Using two different cohorts of medulloblastoma samples, we first studied the expression and methylation profiles of miR-1253. We then explored the anti-tumorigenic properties of miR-1253, in parallel with a biochemical analysis of apoptosis and proliferation, and isolated oncogenic targets using high-throughput screening. Deregulation of miR-1253 expression was noted, both in medulloblastoma clinical samples and cell lines, by epigenetic silencing via hypermethylation; specific de-methylation of miR-1253 not only resulted in rapid recovery of expression but also a sharp decline in tumor cell proliferation and target gene expression. Expression restoration also led to a reduction in tumor cell virulence, concomitant with activation of apoptotic pathways, cell cycle arrest and reduction of markers of proliferation. We identified two oncogenic targets of miR-1253, CDK6 and CD276, whose silencing replicated the negative trophic effects of miR-1253. These data reveal novel tumor-suppressive properties for miR-1253, i.e., (i) loss of expression via epigenetic silencing; (ii) negative trophic effects on tumor aggressiveness; and (iii) downregulation of oncogenic targets.
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| Overall design |
3 normal cell lines, 7 MB cell lines, 15 normal brain control samples, 31 MB tumors samples with subgroup classification
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| Contributor(s) |
Sidharth M |
| Citation(s) |
32145124 |
| Submission date |
Apr 09, 2020 |
| Last update date |
Apr 12, 2020 |
| Contact name |
Pranita Atri |
| Organization name |
UNIVERSITY OF NEBRASKA MEDICAL CENTER
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| Department |
Biochemistry
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| Street address |
S 42nd and Emile St
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| City |
Omaha |
| State/province |
NE |
| ZIP/Postal code |
68198 |
| Country |
USA |
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| Platforms (1) |
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| Samples (56)
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| This SubSeries is part of SuperSeries: |
| GSE148390 |
MiR-1253 exerts tumor-suppressive effects in medulloblastoma via inhibition of CDK6 and CD276 (B7-H3) |
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| Relations |
| BioProject |
PRJNA624127 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE148388_AverageBeta.txt.gz |
49.7 Mb |
(ftp)(http) |
TXT |
| GSE148388_RAW.tar |
941.1 Mb |
(http)(custom) |
TAR (of IDAT) |
| Processed data included within Sample table |
| Processed data are available on Series record |
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