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The biological and prognostic role of long non-coding RNA NEAT1 in acute myeloid leukemia

Miliara, Sophia (författare)
Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden,Andreas Lennartsson
Neddermeyer, Anne (författare)
Uppsala universitet,Institutionen för medicinska vetenskaper,Sören Lehmann
Bonetti, Alessandro (författare)
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan
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Shin, Jay W. (författare)
RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan
Mujahed, Huthayfa (författare)
Department of Medicine, Karolinska Institute, Huddinge, Sweden,Sören Lehmann
Arner, Erik (författare)
Department of Medicine, Karolinska Institute, Huddinge, Sweden; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan,Mikael Ryden
Lehmann, Sören (författare)
Uppsala universitet,Institutionen för medicinska vetenskaper,Department of Medicine, Karolinska Institute, Huddinge, Sweden,Sören Lehmann
Lennartsson, Andreas (författare)
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden,Andreas Lennartsson
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 (creator_code:org_t)
Engelska.
Relaterad länk:
https://urn.kb.se/re...
  • Annan publikation (övrigt vetenskapligt/konstnärligt)
Abstract Ämnesord
Stäng  
  • Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA localized in the cell nucleus that has been associated to promote several malignant solid tumors. Its role in acute myeloid leukemia (AML) remains largely elusive. Therefore, the aim of this study was to define the role of NEAT1 in AML compared to normal hematopoiesis. During normal hematopoiesis, it was identified that NEAT1 expression was low in early progenitors but increased in more differentiated cells, especially in monocytes. NEAT1 expression was increased in AML as a whole compared to normal bone marrow (NBM). It was specifically high in AML with inv(16) and t(8;21), while it was lower in patients with t(15;17). Further, NEAT1 expression correlated positively with ASXL1, KRAS and NRAS mutations and negatively with TP53 mutant AML. Higher NEAT expression was associated to better overall survival in AML, independent of other known risk factors. Antisense oligo-mediated knockdown of NEAT1 in AML cells significantly increased expression of the monocytic marker CD14 while granulocytic markers did not change. Genes affected by NEAT1-knockdown using CAGE-sequencing were significantly enriched for genes involved in glucose metabolism. By investigating genome-wide RNA and DNA interactions using RADICL-sequencing, it was revealed that NEAT1 binds to the loci of key hematopoietic regulator RUNX2 as well as the chromatin regulators KMT2A, KMT5B and CHD7. The results suggest that lncRNA NEAT1 has a potential role in hematopoietic and AML cell differentiation and could be a potential new biomarker in AML.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

acute myeloid leukemia (AML)
hematopoiesis
long non-coding RNAs (lncRNAs)
NEAT1
CAGE-sequencing
RADICL-sequencing
prognosis
Molekylär medicin
Molecular Medicine

Publikations- och innehållstyp

vet (ämneskategori)
ovr (ämneskategori)

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