HOXBLINC is aberrantly expressed in acute myeloid leukemia and functions as a potent oncogenic long non-coding RNA in leukemogenesis

ABSTRACT: 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.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE115096 | GEO | 2021/01/27

REPOSITORIES: GEO