Long noncoding RNA HOTAIR promotes the self-renewal of leukemia stem cells through epigenetic silencing of p15

Experimental Hematology
Shenmeng GaoYanhong Ji

Abstract

Acute myeloid leukemia (AML) is a heterogeneous hematopoietic disorder initiated from a small subset of leukemia stem cell (LSC), which presents unrestricted self-renewal and proliferation. Long non-coding RNA HOTAIR is abundantly expressed and plays oncogenic roles in solid cancer and AML. However, whether HOTAIR regulates the self-renewal of LSC is largely unknown. Here, we reported that the expression of HOTAIR was increased in LSC than in normal hematological stem and progenitor cells (HSPCs). HOTAIR inhibition by short hairpin RNAs (shRNAs) decreased colony formation in leukemia cell lines and primary AML blasts. We then investigated the role of HOTAIR in leukemia in vivo. HOTAIR knockdown extends the survival time in U937-transplanted NSG mice. Furthermore, HOTAIR knockdown reduced infiltration of leukemic blasts, decreased frequency of LSC, and prolonged overall survival in MLL-AF9-induced murine leukemia, suggesting that HOTAIR is required for the maintenance of AML. Mechanistically, HOTAIR inhibited p15 expression through zeste homolog 2 (EZH2)-enrolled tri-methylation of Lys 27 of histone H3 (H3K27me3) in p15 promoter. In addition, p15 partially reversed the decrease of colony and proliferation induced by HOTAIR knock...Continue Reading

Citations

Feb 13, 2019·International Journal of Molecular Sciences·Gabriela Marisol Cruz-MirandaSilvia Jiménez-Morales
Mar 6, 2019·Journal of Cellular Physiology·Mohammad SarfiEhsan Khalili
Oct 2, 2019·Frontiers in Oncology·Alexander A Wurm, Cristina Pina
May 28, 2019·Journal of Hematology & Oncology·Yan LiuLin Fu
Jan 10, 2021·Cancers·Irina A Elcheva, Vladimir S Spiegelman
Mar 1, 2020·European Journal of Pharmacology·Soudeh Ghafouri-FardMohammad Taheri
Mar 31, 2021·Drug Discovery Today·Mehrdad IzadiradZhe-Sheng Chen
Sep 28, 2021·Journal of Cellular Physiology·Anuradha KirtoniaManoj Garg

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