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| Status |
Public on Nov 26, 2014 |
| Title |
Characterization of a network of tumor suppressor microRNA's in T Cell acute lymphoblastic leukemia |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
|
| Summary |
Purpose: The purpose of this study is to identify functionally inter-connected group of miRNAs whose reduced expression promotes leukemia development in vivo. We searched for relevant target genes of these miRNAs that are upregulated in T-ALL relative to controls.
Methods: In order to examine the global gene expression, we generated 9 T-ALL patients and 4 normal controls by deep sequencing using Illumina Hi-Seq sequencer. The sequence reads that passed quality filters were analyzed using Spliced Transcripts Alignment to a Reference aligner (STAR) followed by differential gene expression analysis using DESeq.
Results: Using an optimized data analysis workflow, we mapped reads per sample to the human genome (build hg19) and identified transcripts in both patient and controls with STAR workflow. We applied a machine learning approach to eliminate targets with redundant miRNA-mediated control. This strategy finds a convergence on the Myb oncogene and less prominent effects on the Hpb1 transcription factor. The abundance of both genes is increased in T-ALL and each can promote T-ALL in vivo.
Conclusion: Our study reveals a Myc regulated network of tumor suppressor miRNAs in T-ALL. We identified a small number of functionally validated tumor suppressor miRNAs. These miRNAs are repressed upon Myc activation and this links their expression directly to Myb a key oncogenic driver in T-ALL.
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| Overall design |
Examination of global gene expression in 9 T-ALL patients and 4 normal controls using total RNA sequencing. BaseMeanA in DESeq_results.xlsx is the control.
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| Contributor(s) |
Sanghvi V, Wendel H |
| Citation(s) |
25406379 |
| Submission date |
Nov 24, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Hans-Guido Wendel |
| E-mail(s) |
wendelh@mskcc.org
|
| Phone |
6468882528
|
| Organization name |
Sloan Kettering Cancer Center
|
| Street address |
1275 York Avenue
|
| City |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
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| Samples (13)
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| Relations |
| BioProject |
PRJNA268382 |
| SRA |
SRP050223 |
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