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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F18%3A10427541" target="_blank" >RIV/00064203:_____/18:10427541 - isvavai.cz</a>

Alternative codes found

RIV/65269705:_____/18:00069101 RIV/00216224:14740/18:00105661 RIV/00216208:11110/18:10384245 RIV/00216208:11120/18:43917064 and 3 more

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=U4~iq_oMNU" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=U4~iq_oMNU</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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30205 - Hematology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

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

Name of the periodical

Blood

ISSN

0006-4971

e-ISSN

—

Volume of the periodical

132

Issue of the periodical within the volume

22

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

2389-2400

UT code for WoS article

000451634400012

EID of the result in the Scopus database

2-s2.0-85057234268