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| Status |
Public on Jan 27, 2021 |
| Title |
HOXBLINC is aberrantly expressed in acute myeloid leukemia and functions as a potent oncogenic long non-coding RNA in leukemogenesis |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
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| Summary |
Dysregulation of HOXA/B genes is a dominant mechanism of leukemic transformation.HOXB locus-associated long non-coding RNA (lncRNAs), HOXBLINC, regulates transcription of the anterior HOXB genes and plays a critical role in hematopoiesis development. Here, we show that HOXBLINC lncRNA is up-regulated in over 60% of patients with AML. Interestingly, AML patients with high HOXBLINC expression have a significantly shortened survival as compared to low HOXBLINC expressing patients. Transgenic expression of HoxBlinc in mice leads to dramatically increased pools of long-term (LT)- and short-term (ST)-hematopoietic stem cells (HSCs) and development of AML. Mechanistically, HoxBlinc overexpression alters the expression of genes (including HoxB1-6, Met, Meis1, Cdx2,HoxA9,Runx1, Irf8 and Wnt5a) critical for HSC regulation and/or leukemogenesis,and enhances enhancer/promoter chromatin accessibility in these loci. Importantly, knockdown of HOXBLINC suppresses OCI-AML3 leukemic cell proliferation both in vitro and in vivo through abrogating the aberrant expression of HOXB and other leukemogenic genes. Our study identifies HOXBLINC as a potent oncogenic lncRNA in leukemogenesis, which coordinate to maintain an oncogenic transcription program for leukemic transformation. Our study also provides novel insights into the HSC regulation by lncRNAs.
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| Overall design |
RNA-SEQ, ATAC-seq, ChIP-seq and 4C-seq were carried out with WT and Hoxblinc transgenic mice cells.LSK cells (Lin- Sca1+ Kit+) were sorted by FACS from the bone marrow of WT and HoxBlinc transgenic mice for RNA-seq and ATAC-seq assay, and similarly, LK cells (Lin- Kit+) were sorted for CHIP-seq and 4C assay.
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| Contributor(s) |
Huang S, Xu M, Luo H, Zhu G |
| Citation(s) |
33782403 |
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| Submission date |
May 30, 2018 |
| Last update date |
Apr 20, 2021 |
| Contact name |
Suming Huang |
| E-mail(s) |
[email protected]
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| Organization name |
Penn State University
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| Department |
Pediatrics
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| Street address |
500 University Dr.
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| City |
Hershey |
| State/province |
PA |
| ZIP/Postal code |
17033 |
| Country |
USA |
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| Platforms (5)
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| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (40)
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| Relations |
| BioProject |
PRJNA473783 |
| SRA |
SRP149346 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE115096_RAW.tar |
6.6 Mb |
(http)(custom) |
TAR (of BED, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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