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miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels

Identifikátory výsledku

  • Kód výsledku v IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F18%3A00069101" target="_blank" >RIV/65269705:_____/18:00069101 - isvavai.cz</a>

  • Nalezeny alternativní kódy

    RIV/00216224:14740/18:00105661 RIV/00216208:11110/18:10384245 RIV/00216208:11120/18:43917064 RIV/00064173:_____/18:N0000151 a 3 dalších

  • Výsledek na webu

    <a href="http://dx.doi.org/10.1182/blood-2018-06-855502" target="_blank" >http://dx.doi.org/10.1182/blood-2018-06-855502</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1182/blood-2018-06-855502" target="_blank" >10.1182/blood-2018-06-855502</a>

Alternativní jazyky

  • Jazyk výsledku

    angličtina

  • Název v původním jazyce

    miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels

  • Popis výsledku v původním jazyce

    Follicular lymphoma (FL) is a common indolent B-cell malignancy with a variable clinical course. An unfavorable event in its course is histological transformation to a high-grade lymphoma, typically diffuse large B-cell lymphoma. Recent studies show that genetic aberrations ofMYC or its overexpression are associated with FL transformation (tFL). However, the precise molecular mechanisms underlying tFL are unclear. Here we performed the first profiling of expression of microRNAs (miRNAs) in paired samples of FL and tFL and identified 5 miRNAs as being differentially expressed. We focused on one of these miRNAs, namely miR-150, which was uniformly downmodulated in all examined tFLs (similar to 3.5-fold), and observed that high levels of MYC are responsible for repressing miR-150 in tFL by binding in its upstream region. This MYC-mediated repression of miR-150 in B cells is not dependent on LIN28A/B proteins, which influence the maturation of miR-150 precursor (pri-miR-150) in myeloid cells. We also demonstrated that low miR-150 levels in tFL lead to upregulation of its target, namely FOXP1 protein, which is a known positive regulator of cell survival, as well as B-cell receptor and NF-kappa B signaling in malignant B cells. We revealed that low levels of miR-150 and high levels of its target, FOXP1, are associated with shorter overall survival in FL and suggest that miR-150 could serve as a good biomarker measurable in formalin-fixed paraffin-embedded tissue. Overall, our study demonstrates the role of theMYC/miR-150/FOXP1 axis in malignant B cells as a determinant of FL aggressiveness and its high-grade transformation.

  • Název v anglickém jazyce

    miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels

  • Popis výsledku anglicky

    Follicular lymphoma (FL) is a common indolent B-cell malignancy with a variable clinical course. An unfavorable event in its course is histological transformation to a high-grade lymphoma, typically diffuse large B-cell lymphoma. Recent studies show that genetic aberrations ofMYC or its overexpression are associated with FL transformation (tFL). However, the precise molecular mechanisms underlying tFL are unclear. Here we performed the first profiling of expression of microRNAs (miRNAs) in paired samples of FL and tFL and identified 5 miRNAs as being differentially expressed. We focused on one of these miRNAs, namely miR-150, which was uniformly downmodulated in all examined tFLs (similar to 3.5-fold), and observed that high levels of MYC are responsible for repressing miR-150 in tFL by binding in its upstream region. This MYC-mediated repression of miR-150 in B cells is not dependent on LIN28A/B proteins, which influence the maturation of miR-150 precursor (pri-miR-150) in myeloid cells. We also demonstrated that low miR-150 levels in tFL lead to upregulation of its target, namely FOXP1 protein, which is a known positive regulator of cell survival, as well as B-cell receptor and NF-kappa B signaling in malignant B cells. We revealed that low levels of miR-150 and high levels of its target, FOXP1, are associated with shorter overall survival in FL and suggest that miR-150 could serve as a good biomarker measurable in formalin-fixed paraffin-embedded tissue. Overall, our study demonstrates the role of theMYC/miR-150/FOXP1 axis in malignant B cells as a determinant of FL aggressiveness and its high-grade transformation.

Klasifikace

  • Druh

    J<sub>imp</sub> - Článek v periodiku v databázi Web of Science

  • CEP obor

  • OECD FORD obor

    30205 - Hematology

Návaznosti výsledku

  • Projekt

    Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

  • Návaznosti

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Ostatní

  • Rok uplatnění

    2018

  • Kód důvěrnosti údajů

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Údaje specifické pro druh výsledku

  • Název periodika

    Blood

  • ISSN

    0006-4971

  • e-ISSN

  • Svazek periodika

    132

  • Číslo periodika v rámci svazku

    22

  • Stát vydavatele periodika

    US - Spojené státy americké

  • Počet stran výsledku

    12

  • Strana od-do

    2389-2400

  • Kód UT WoS článku

    000451634400012

  • EID výsledku v databázi Scopus

    2-s2.0-85057234268