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HOTTIP lncRNA Promotes Hematopoietic Stem Cell Self-Renewal Leading to AML-like Disease in Mice.

Abstract：

:Long non-coding RNAs (lncRNAs) are critical for regulating HOX genes, aberration of which is a dominant mechanism for leukemic transformation. How HOX gene-associated lncRNAs regulate hematopoietic stem cell (HSC) function and contribute to leukemogenesis remains elusive. We found that HOTTIP is aberrantly activated in acute myeloid leukemia (AML) to alter HOXA-driven topologically associated domain (TAD) and gene expression. HOTTIP loss attenuates leukemogenesis of transplanted mice, while reactivation of HOTTIP restores leukemic TADs, transcription, and leukemogenesis in the CTCF-boundary-attenuated AML cells. Hottip aberration in mice abnormally promotes HSC self-renewal leading to AML-like disease by altering the homeotic/hematopoietic gene-associated chromatin signature and transcription program. Hottip aberration acts as an oncogenic event to perturb HSC function by reprogramming leukemic-associated chromatin and gene transcription.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Luo H,Zhu G,Xu J,Lai Q,Yan B,Guo Y,Fung TK,Zeisig BB,Cui Y,Zha J,Cogle C,Wang F,Xu B,Yang FC,Li W,So CWE,Qiu Y,Xu M,Huang S

doi

10.1016/j.ccell.2019.10.011

subject

Has Abstract

pub_date

2019-12-09 00:00:00

pages

645-659.e8

issue

6

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(19)30485-4

journal_volume

36

pub_type

杂志文章

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