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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

LEF1-AS1, long non-coding RNA, inhibits proliferation in myeloid malignancy

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Autor(es):
Congrains-Castillo, Ada [1] ; Niemann, Fernanda S. [1] ; Duarte, Adriana S. Santos [1] ; Olalla-Saad, Sara T. [1]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas, Hemoctr, Hematol & Hemotherapy Ctr, Sao Paulo - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE; v. 23, n. 4, p. 3021-3025, APR 2019.
Citações Web of Science: 0
Resumo

LEF1 antisense RNA 1 (LEF1-AS1) is an antisense long non-coding RNA encoded in the lymphoid enhancer-binding factor 1 (LEF1) locus. LEF1-AS1 is a conserved transcript dysregulated in hematopoiesis. This study aimed to functionally characterize the role of this transcript in myeloid malignancy and explore a possible regulatory effect of LEF1-AS1 upon LEF1. We show that LEF1-AS1 is highly expressed in normal hematopoietic stem cells but barely detectable in myeloid malignant cell lines. Additionally, bone marrow cells from myelodysplastic syndrome (n=12) and acute myeloid malignancy patients (n=28) expressed significantly reduced levels of LEF1-AS1 compared to healthy controls (n=15). Artificial LEF1-AS1 over-expression inhibited proliferation in HL60 and led to an upregulation of tumor suppressors p21 and p27, and reduced ERK1/2 activation. Unexpectedly, no underlying modulation of LEF1 was detected. Ectopic expression of LEF1-AS1 also inhibited proliferation in HELA, a cell line lacking endogenous expression of LEF1, supporting a LEF1-independent mechanism. Additionally, transient over-expression of LEF1-AS1 in AML patient cells also led to reduced proliferation and colony formation capacity. We used a mass spectrometry-based proteomics approach. Proteomic quantification identified the modulation of an important metabolic regulator, Fumarase, and concomitant accumulation of the metabolite fumarate. (AU)

Processo FAPESP: 13/17227-8 - RNAs não-codificadores na síndrome mielodisplásica (SMD)
Beneficiário:Ada Congrains Castillo
Linha de fomento: Bolsas no Brasil - Pós-Doutorado