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Series GSE115096 Query DataSets for GSE115096
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
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.
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.
Contributor(s) Huang S, Xu M, Luo H, Zhu G
Citation(s) 33782403
Submission date May 30, 2018
Last update date Apr 20, 2021
Contact name Suming Huang
Organization name Penn State University
Department Pediatrics
Street address 500 University Dr.
City Hershey
State/province PA
ZIP/Postal code 17033
Country USA
Platforms (5)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (40)
GSM3165084 WT-RNA-seq-1
GSM3165085 WT-RNA-seq-2
GSM3165086 Hoxblinc-Tg-RNA-seq-1
BioProject PRJNA473783
SRA SRP149346

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Supplementary file Size Download File type/resource
GSE115096_RAW.tar 6.6 Mb (http)(custom) TAR (of BED, TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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